WO2025181810A1

WO2025181810A1 - Botanical antiviral composition

Info

Publication number: WO2025181810A1
Application number: PCT/IL2025/050199
Authority: WO
Inventors: Dorit Arad
Original assignee: Nlc Pharma Ltd
Current assignee: Nlc Pharma Ltd
Priority date: 2024-03-01
Filing date: 2025-02-27
Publication date: 2025-09-04
Anticipated expiration: 2026-09-01

Abstract

The present invention provides compositions comprising extracts from specific plant genera or alternatives thereof, including Lithospermum and Oryza or alternatives thereof, along with optional extracts from Scutellaria and Boswellia. The compositions thus include shikonin, anthocyanins, and other bioactive compounds such as flavonoids and boswellic acids. Additional ingredients like ivermectin, metformin, and curcumin may be incorporated. The compositions are designed as multi-targeted therapeutic agents, combining viral protease inhibitors, endogenous host protease inhibitors, anti-inflammatory agents, and anti-senescence agents. These compositions are intended for treating various medical conditions, including respiratory diseases, viral infections, inflammatory conditions, immune-related disorders, liver conditions, and neurological conditions. The invention describes methods of treatment and use in manufacturing medicaments for these conditions.

Description

BOTANICAL ANTIVIRAL COMPOSITION

RELATED APPLICATION

This application claims the benefit of priority of U.S. Provisional Patent Application No. 63/559,886 filed on 1 March 2024, the content of which is incorporated herein by reference in their entirety.

FIELD AND BACKGROUND OF THE INVENTION

The present invention, in some embodiments thereof, relates to healthcare supplements, and more particularly, but not exclusively, to plant-based compositions for treating various infections and inflammations.

Infections and inflammations have long been significant health concerns, posing substantial challenges to medical professionals and patients alike. The ongoing search for effective remedies has led researchers to explore various natural compounds and extracts for their potential therapeutic properties. In recent years, there has been a growing interest in plant-derived substances, particularly those with antiviral and anti-inflammatory properties, as potential treatments for a wide range of diseases.

The state of the art in this field has primarily focused on individual compounds or extracts with specific activities. However, there has been a long-felt need for a more comprehensive approach that addresses both the viral infection and the associated inflammatory response simultaneously. This multi-action approach could potentially provide more effective treatment options for patients suffering from various viral infections and related inflammatory conditions.

One area of particular interest has been the exploration of shikonin and its derivatives, which have shown promise in previous studies for their antiviral and anti-inflammatory properties. However, the full potential of these compounds and related plant extracts has not been fully realized, especially in the context of treating complex viral infections that often involve severe inflammatory responses.

Additionally, there has been a growing recognition of the importance of bioavailability in the effectiveness of natural compounds. Many potentially beneficial substances face challenges in terms of absorption and distribution within the body, limiting their therapeutic potential. This has created a need for innovative formulations that can enhance the bioavailability and effective concentration of active compounds, thereby improving their overall efficacy.

Furthermore, the recent global health challenges have highlighted the urgent need for novel antiviral treatments that can effectively combat emerging viral threats while also addressing the often severe inflammatory responses associated with these infections. This has led to increased interest in natural compounds and extracts that may offer multiple mechanisms of action, potentially providing more comprehensive treatment options.

In light of these challenges and unmet needs, there is a clear opportunity for the development of new therapeutic approaches that combine antiviral activity with potent antiinflammatory effects and preventing the damages associated with senescence. Such innovations could potentially address the long-standing need for more effective and multifaceted treatments for viral infections and associated inflammatory conditions, offering hope for improved patient outcomes and reduced disease burden.

SUMMARY OF THE INVENTION

According to one aspect of the present invention, there is provided a composition comprising: extract of plant A of a genus selected from the group consisting of Lithospermum, Arnebia, Coleus, Plectranthus, and Solenostemom, and extract of plant B of a genus selected from the group consisting of Oryza, Aronia, Vaccinium, Rubus, Prunus, Vitis, Solanum, Malus, Brassica, Dioscorea, Sambucus, Ribes, Fragaria, Citrus, and Ipomoea.

In at least one embodiment, plant A is of a Lithospermum genus.

In at least one embodiment, plant A is gromwell (Lithospermum erythrorhizori).

In at least one embodiment, the amount of said extract of plant A ranges 30-60 %wt of the total weight of the composition.

In at least one embodiment, plant B is of a Oryza genus.

In at least one embodiment, plant B is black rice (Oryza sativa L).

In at least one embodiment, the amount of said extract of plant B ranges 30-60 %wt of the total weight of the composition.

In at least one embodiment, the composition further includes at least one of: extract of plant C of a genus Scutellaria', and extract of plant D of a genus Boswellia.

In at least one embodiment, plant C is Scutellaria baicalensis.

In at least one embodiment, the amount of the extract of plant C ranges 10-40 %wt of the total weight of the composition.

In at least one embodiment, plant D is selected from the group consisting of Boswellia sacra, Boswellia serrata, Boswellia papyrifera and Boswellia carteri. In at least one embodiment, the amount of the extract of plant D ranges 20-60 %wt of the total weight of the composition.

According to one aspect of the present invention, there is provided a composition includes: a shikonin; and an anthocyanin.

In at least one embodiment, the amount of the shikonin ranges 2-15 %wt of the total weight of the composition.

In at least one embodiment, the amount of the anthocyanin ranges 30-50 %wt of the total weight of the composition.

In at least one embodiment, the composition further includes at least one flavonoid selected from the group consisting of baicalin, baicalein, and wogonin.

In at least one embodiment, the composition further includes at least one boswellic acid selected from the group consisting of incensole, incensole acetate, a-boswellic acid, P-boswellic acid, acetyl-P-boswellic acid, 11-keto-P-boswellic acid (KB A), acetyl- 11-keto-P-boswellic acid (AKBA), 3-O-acetyl-a-boswellic acid, 3-O-acetyl-P-boswellic acid, 3-O-acetyl-l l-keto-P- boswellic acid, lupeolic acid, and 3-O-acetyl-lupeolic acid.

In at least one embodiment, the composition further includes at least one of: ivermectin; metformin; curcumin/nano-curcumin; and aspirin.

In at least one embodiment, the amount of the ivermectin ranges 0.1-10 %wt of the total weight of the composition.

In at least one embodiment, the amount of the metformin ranges 25-50 %wt of the total weight of the composition.

In at least one embodiment, the amount of the nano-curcumin ranges 5-10 %wt of the total weight of the composition.

In at least one embodiment, the composition further includes a lipid.

In at least one embodiment, the lipid is selected from the group consisting of a glycerophospholipid, a sphingolipids and/or a sterol.

In at least one embodiment, the glycerophospholipid is selected from the group consisting of phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol, phosphatidic acid, sphingomyelin and cholesterol.

In at least one embodiment, the source of the lipid is lecithin. In at least one embodiment, the amount of the lipid ranges 5-15 %wt of the total weight of the composition.

According to one aspect of the present invention, there is provided a composition that includes: a viral protease inhibitor; an endogenous host protease inhibitor; an anti-inflammatory agent; and an anti-senescence agent.

In at least one embodiment, the viral protease is selected from the group consisting of a 3CL protease inhibitor such as baicalin, baicalein, quercetin, epigallocatechin gallate (EGCG), curcumin/nano-curcumin, glycyrrhizin, and shikonin; a flavonoid such as quercetin, baicalein, and myricetin; a polyphenol such as epigallocatechin gallate (EGCG), resveratrol, and curcumin/nano- curcumin; a stilbenoid such as pterostilbene, hopeaphenol, and trans-s-viniferin; a lignan such as arctigenin, sesamin, and podophyllo toxin; an alkaloid such as berberine, camptothecin, and sanguinarine; a terpenoid such as glycyrrhizin, andrographolide, and betulinic acid; a quinone such as shikonin, tanshinone IIA, and emodin; a coumarin such as esculetin, psoralen, and scopoletin; a chaicone such as xanthohumol, licochalcone A, and isoliquiritigenin; a tannin such as punicalagin, chebulagic acid, and ellagic acid; a saponin such as ginsenoside Rg3, saikosaponin D, and astragaloside IV; a carotenoid such as lutein, lycopene, and P-carotene; an anthocyanin such as cyanidin, delphinidin, and malvidin; a sulfur-containing compound such as allicin, sulforaphane, and S-allyl cysteine; a peptide-based inhibitor such as cyclotide, lunasin, and sunflower trypsin inhibitor.

In at least one embodiment, the viral protease is 3CL protease, and the viral protease inhibitor is an anthocyanin and/or shikonin.

In at least one embodiment, the endogenous host protease inhibitor is selected from the group consisting of a cysteine protease inhibitor such as shikonin, tanshinone IIA, and betulinic acid; a flavonoid such as quercetin, kaempferol, baicalin, and baicalein; a polyphenol such as epigallocatechin gallate (EGCG), curcumin/nano-curcumin, and resveratrol; a stilbenoid such as pterostilbene, hopeaphenol, and trans-s-viniferin; a lignan such as arctigenin, sesamin, and podophyllo toxin; an alkaloid such as berberine, chelerythrine, and sanguinarine; a terpenoid such as boswellic acid, glycyrrhizin, and andrographolide; a quinone such as shikonin, tanshinone IIA, and emodin; a coumarin such as esculetin, psoralen, and scopoletin; a chaicone such as xanthohumol, licochalcone A, and isoliquiritigenin; a tannin such as punicalagin, chebulagic acid, and ellagic acid; a saponin such as ginsenoside Rg3, saikosaponin D, and astragaloside IV; a carotenoid such as lutein, lycopene, and P-carotene; an anthocyanin such as cyanidin, delphinidin, and malvidin; a sulfur-containing compound such as allicin, sulforaphane, and S-allyl cysteine; a peptide-based inhibitor such as cyclotide, lunasin, and sunflower trypsin inhibitor; a serine protease inhibitor such as boswellic acid, glycyrrhizin, and epigallocatechin gallate (EGCG); a matrix metalloproteinase (MMP) inhibitor such as curcumin/nano-curcumin, resveratrol, and baicalein; an elastase inhibitor such as a boswellic acid, frankincense resin, quercetin, and kaempferol.

In at least one embodiment, the endogenous host protease is transmembrane serine protease 5, and the endogenous host protease inhibitor is an anthocyanin, a boswellic acid and/or shikonin.

In at least one embodiment, the anti-inflammatory agent is selected from the group consisting of a flavonoid such as quercetin, kaempferol, baicalin and baicalein; a polyphenol such as epigallocatechin gallate (EGCG), resveratrol, and curcumin; a stilbenoid such as pterostilbene, hopeaphenol, and trans-s-viniferin; a lignan such as arctigenin, sesamin, and podophyllo toxin; an alkaloid such as berberine, chelerythrine, and sanguinarine; a terpenoid such as frankincense terpenoids, boswellic acids, and andrographolide; a quinone such as shikonin, tanshinone IIA, and emodin; a coumarin such as esculetin, psoralen, and scopoletin; a chaicone such as xanthohumol, licochalcone A, and isoliquiritigenin; a tannin such as punicalagin, chebulagic acid, and ellagic acid; a saponin such as ginsenoside Rg3, saikosaponin D, and astragaloside IV; a carotenoid such as lutein, lycopene, and P-carotene; an anthocyanin such as cyanidin, delphinidin, and malvidin; a sulfur-containing compound such as allicin, sulforaphane, and S-allyl cysteine; a peptide-based anti-inflammatory agent such as cyclotide, lunasin, and sunflower trypsin inhibitor; a nuclear factor-kappa B (NF-KB) inhibitor such as frankincense, curcumin, and andrographolide; a cytokine modulator such as quercetin, resveratrol, and baicalein; an inflammasome inhibitor such as curcumin/nano-curcumin, epigallocatechin gallate (EGCG), and tanshinone IIA; a cyclooxygenase (COX) inhibitor such as nano-curcumin, boswellic acids, and licochalcone A; a lipoxygenase (LOX) inhibitor such as anthocyanins, luteolin, and myricetin.

In at least one embodiment, the anti-inflammatory agent is an anthocyanin, a boswellic acid such as incensole/incensole acetate and/or curcumin/nano-curcumin.

In at least one embodiment, the anti-senescence agent is selected from the group consisting of a telomerase activator such as cycloastragenol, astragaloside IV, and Telomerase Activator 2 (TAT2); a senolytic agent such as quercetin, fisetin, and piperlongumine; an mTOR inhibitor such as metformin, rapamycin (sirolimus), everolimus, and resveratrol; an NAD+ booster such as nicotinamide riboside, nicotinamide mononucleotide (NMN), and niacin (vitamin B3); a sirtuin activator such as resveratrol, pterostilbene, and fisetin; an antioxidant and free radical scavenger such as vitamin C, vitamin E, and coenzyme Q10; a DNA repair enhancer such as shikonin, nicotinamide, Oxoguanine Glycosylase 1 (OGGI) activators, and Poly (ADP-ribose) Polymerase inhibitors (PARP inhibitors); an autophagy inducer such as spermidine, curcumin/nano-curcumin, and urolithin A; a mitochondrial function enhancer such as pyrroloquinoline quinone (PQQ), Mitoquinone (MitoQ), and SS-31 (elamipretide); an epigenetic modulator such as valproic acid, sodium butyrate, and epigallocatechin gallate (EGCG); a stem cell activator such as SB203580 (p38 Mitogen- Activated Protein Kinase inhibitor), Y-27632 (Rho-associated protein kinase inhibitor), and fucoidan; an inflammasome inhibitor such as MCC950, OLT1177, and tranilast; a senescence-associated secretory phenotype (SASP) inhibitor such as glucocorticoids, Janus Kinase inhibitors (JAK inhibitors) (ruxolitinib, tofacitinib), and apigenin; a proteostasis regulator such as 17- Allylamino- 17-demethoxygeldanamycin (17-AAG, tanespimycin), 17-Demethoxy-17- allylamino-geldanamycin (17-DMAG, alvespimycin), and arimoclomol; a cellular reprogramming factor such as octamer-binding transcription factor 4 (Oct4), sex-determining region Y-box 2 (Sox2), and Kruppel-like factor 4 (Klf4); a hormone replacement/modulator such as growth hormone, dehydroepiandrosterone (DHEA), and melatonin; an extracellular matrix (ECM) modulator such as hyaluronic acid, collagen peptides, and glucosamine; a caloric restriction mimetic such as 2-deoxyglucose, hydroxycitrate, and spermidine; an exercise mimetic such as 5- Aminoimidazole-4-carboxamide ribonucleotide (AICAR), GW501516, and SR9009; a genomic stability enhancer such as nuclear receptor binding to intronic DNA (NR-BID), LB-100 (Protein Phosphatase 2A inhibitor, PP2A inhibitor), and an anthocyanin.

In at least one embodiment, the anti-senescence agent is shikonin, metformin and/or an anthocyanin.

In at least one embodiment, the composition is for use in the treatment of a medical condition in a subject in need thereof.

According to one aspect of the present invention, there is provided a use of the composition provided herein, for the manufacturing in the treatment of a medical condition in a subject in need thereof.

According to one aspect of the present invention, there is provided a method of treating a medical condition, includes administering to a subject in need thereof a therapeutically effective amount of any one of the compositions of the preceding claims.

In at least one embodiment, the medical condition is selected from the group consisting of a respiratory disease such as COVID-19, SARS, and MERS; a viral infection such as influenza, RSV, and human coronaviruses (hCoV-HKUl, hCoV-NL63, hCoV-229E); an inflammatory condition such as lung inflammation, cytokine storm, and excessive immune response; an immune- related disorder such as viral-induced immune dysfunction, excessive NLRP3 inflammasome activation, and inflammatory stress; a liver condition such as liver dysfunction and viral-induced hepatic stress; a neurological condition such as cognitive dysfunction and neural inflammation.

According to one aspect of the present invention, there is provided a medical food, includes or consisting of the composition of any preceding claim.

DESCRIPTION OF EMBODIMENTS OF THE INVENTION

Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details set forth in the following description or exemplified by the Examples. The disclosure is meant to encompass other embodiments or of being practiced or carried out in various ways.

While conceiving the present invention, the present inventors envisioned compositions and methods for treating and preventing viral infections, particularly those affecting the respiratory system. The inventors have conceived an innovative multi-action approach based on the combination of several key ingredients, each targeting different aspects of viral pathogenesis and host response. This approach culminates in a composition comprising a viral protease inhibitor, an endogenous host protease inhibitor, an anti-inflammatory agent, and an anti-senescence agent. The synergistic interplay of these components addresses multiple facets of viral infections, potentially offering improved efficacy compared to traditional single-target therapies.

In the course of reducing the present invention to practice, the inventors have made a surprising and unexpected discovery. The combination of shikonin and anthocyanins, along with certain optional ingredients in the claimed composition, exhibits a synergistic effect that significantly enhances the overall therapeutic potential of the formulation. This synergy surpasses the individual effects of the components, resulting in a more potent and efficacious treatment than could be predicted from the properties of each ingredient alone. This remarkable finding underscores the innovative nature of the present invention and its potential to advance the field of antiviral therapeutics. This unexpected synergy between shikonin and anthocyanin represents a significant advancement in the field, potentially leading to more effective treatments for viral respiratory infections.

The present invention thus provides a comprehensive solution to combat viral infections by simultaneously targeting viral replication, modulating host immune response, reducing inflammation, and mitigating cellular senescence. This multi-pronged strategy may offer advantages in terms of efficacy, reduced risk of viral resistance, and potential application across a broad spectrum of viral pathogens. The following specification describes the invention in detail, including its components, methods of preparation, and potential therapeutic applications.

The present invention employs a "multi-warhead" approach to address the treatment of medical conditions, particularly those with complex pathophysiologies such as viral infections and their associated complications. This strategy leverages the synergistic effects achieved by combining active ingredients that target multiple mechanisms of therapeutic action simultaneously. By addressing a medical condition from more than one angle, the composition creates a synergistic effect that is greater than the sum of its individual components. This multiwarhead approach can be likened to a precision-guided therapeutic intervention, where each "warhead" targets a specific aspect of the disease process. For example, in the context of viral infections, one warhead might target viral replication, another might modulate the immune response, while a third addresses inflammation, and a fourth supports cellular repair and regeneration. The synergy between these different mechanisms of action can potentially lead to enhanced efficacy, reduced likelihood of treatment resistance, and a more comprehensive management of the condition. This approach is particularly valuable in addressing complex, multifaceted medical conditions where single-target therapies may fall short. By simultaneously engaging multiple therapeutic pathways, the multi-warhead strategy aims to provide a more robust and adaptable therapeutic response, potentially improving clinical outcomes and patient wellbeing. Furthermore, this synergistic approach may allow for lower doses of individual components, potentially reducing the risk of side effects while maintaining or even enhancing therapeutic efficacy.

A plant-based composition:

In this aspect of the invention, the composition is defined in terms of plant extracts rather than isolated active ingredients. Specifically, the composition comprises at least two key plant extracts: one rich in shikonin and another rich in anthocyanins. The combination of these plant extracts in the composition leverages the complementary and potentially synergistic effects of their bioactive compounds as well as the beneficial entourage effect. Both extracts exhibit antiinflammatory and antiviral properties through distinct yet potentially overlapping mechanisms, which may enhance the overall therapeutic efficacy of the composition. This plant extract-based approach to defining the composition allows for the inclusion of a complex array of naturally occurring compounds, potentially leading to a more holistic therapeutic effect. The use of whole plant extracts may also provide additional beneficial compounds that work in concert with shikonin and anthocyanins, potentially enhancing their bioavailability or efficacy. While this approach may introduce some variability in the exact composition, it maintains the integrity of the plant's natural phytochemical profile, which may contribute to the overall effectiveness of the formulation.

The use of plant extracts in this composition, rather than isolated bioactive ingredients, takes advantage of the beneficial entourage effect. This phenomenon, well-recognized in phytotherapy, refers to the synergistic interaction between multiple compounds present in a plant extract, resulting in enhanced therapeutic effects compared to isolated compounds. In the context of this invention, the entourage effect may manifest through various mechanisms. For instance, secondary metabolites present in the shikonin-rich extract may enhance the bioavailability or stability of shikonin itself. Similarly, the anthocyanin-rich extract likely contains other flavonoids and phenolic compounds that may potentiate the effects of anthocyanins or provide complementary activities. Furthermore, the presence of diverse phytochemicals in these extracts may target multiple biological pathways simultaneously, potentially leading to a more comprehensive therapeutic action. This multi-compound, multi-target approach aligns with the complex nature of many health conditions and may offer advantages in terms of efficacy and reduced likelihood of developing resistance to treatment. The entourage effect also acknowledges the intricate balance of compounds naturally present in plants, which may have evolved to work in concert for optimal biological activity. By preserving this natural complexity, the composition harnesses the full potential of the plant materials, potentially offering a more holistic and effective therapeutic solution.

According to some embodiments of the present invention, there is provided a composition that act in synergy to improve health and fight infections, which includes at least the following substances: extract of plant A of a genus selected from the group consisting of Lithospermum, Arnebia, Coleus, Plectranthus, and Solenostemorr, and extract of plant B of a genus selected from the group consisting of Oryza, Aronia, Vaccinium, Rubus, Prunus, Vitis, Solarium, Malus, Brassica, Dioscorea, Sambucus, Ribes, Fragaria, Citrus, and Ipomoea.

The genii Lithospermum, Amebia, Coleus, Plectranthus, and Solenostemon share several beneficial therapeutic substances, primarily due to their rich phytochemical profiles. These plant genera are known for containing various bioactive compounds that contribute to their medicinal properties. One of the most significant commonalities among these genera is the presence of naphthoquinones, particularly shikonin and its derivatives. Shikonin is a potent compound known for its anti-inflammatory, antimicrobial, antiviral and antitumor properties. Additionally, these plants often contain polyphenols, flavonoids, and terpenoids, which contribute to their antioxidant and anti-inflammatory effects. Many species within these genera also produce rosmarinic acid, a compound with notable antioxidant and neuroprotective properties. Tanshinones, found in some species of these genera, particularly in Lithospermum, have demonstrated cardiovascular protective effects. Some species also contain alkaloids that have shown potential in treating various ailments. It is noted that the genus Onosma, which is closely related to Lithospermum and Arnebia, also shares many of these beneficial compounds, particularly shikonin and its derivatives. The genera Salvia and Origanum, while not mentioned in the original list, also share some of these beneficial substances, especially rosmarinic acid and other polyphenols. These plants have been used in traditional medicine systems across different cultures for centuries, and modern research continues to uncover and validate their therapeutic potential. The presence of these diverse bioactive compounds makes these plant genera valuable sources for the development of natural therapeutics and nutraceuticals.

The genii Oryza, Aronia, Vaccinium, Rubus, Prunus, Vitis, Solanum, Malus, Brassica, Dioscorea, Sambucus, Ribes, Fragaria, Citrus, and Ipomoea share several beneficial therapeutic substances, primarily due to their rich phytochemical profiles. These plant genera are known for containing various bioactive compounds that contribute to their medicinal properties. One of the most significant commonalities among these genera is the presence of polyphenols, particularly anthocyanins and flavonoids. These compounds are powerful antioxidants that help protect cells from oxidative stress and have anti-inflammatory properties. Many of these genera, especially those producing colorful fruits like Aronia, Vaccinium, Rubus, and Vitis, are rich sources of anthocyanins, which give berries their distinctive colors and have been associated with various health benefits, including cardiovascular protection and potential anti-cancer effects. Vitamin C is another common beneficial substance found in many of these genera, particularly in Citrus, Ribes, and Fragaria. This essential vitamin acts as an antioxidant and supports immune function. Several of these genera, including Brassica and Solanum, contain glucosinolates, which are sulfur- containing compounds known for their potential anti-cancer properties. Carotenoids, such as betacarotene and lycopene, are present in many of these plants, particularly in Solanum and some Citrus species, contributing to eye health and overall antioxidant status. Dietary fiber is a common beneficial substance across many of these genera, supporting digestive health and potentially reducing the risk of chronic diseases. Some genera, like Dioscorea, are rich in complex carbohydrates and may contain unique compounds like diosgenin, a precursor for the synthesis of various steroid hormones. Ellagic acid and other ellagitannins are found in high concentrations in genera like Rubus and Fragaria, known for their antioxidant and potential anti-cancer properties. Many of these plants also contain essential minerals and trace elements that are crucial for various bodily functions. The presence of these diverse bioactive compounds makes these plant genera valuable sources for the development of natural therapeutics, nutraceuticals, and functional foods such as medicinal foods, with potential applications in preventing and managing various health conditions.

The process of obtaining extracts from plants of the aforementioned genera and related species involves various extraction methods, each designed to isolate and/or concentrate specific bioactive compounds. The selection of an appropriate extraction method depends on the desired compounds, their chemical properties, and the intended use of the extract. Generally, the process begins with the collection and preparation of plant material, which may include roots, leaves, stems, bark, fruits, seeds or flowers. In addition to roots, leaves, stems, bark, fruits, seeds, and flowers, another essential part of plants is the buds, which are undeveloped shoots that can grow into new leaves or flowers. Additionally, petioles are important as they connect the leaves to the stems and support their structure. Nodes are also significant, as they are the points on the stem where leaves and buds emerge. Lastly, chloroplasts play a crucial role in photosynthesis, allowing plants to convert sunlight into energy. Together, these parts contribute to the overall growth and functionality of plants in their ecosystems.

The plant material is typically dried and ground to increase surface area and facilitate extraction. Aqueous extraction is one of the simplest methods, involving the use of water as a solvent. This method is particularly effective for extracting water-soluble compounds such as polyphenols and some alkaloids. The plant material is mixed with water, often heated to increase solubility, and then filtered to separate the liquid extract from the solid residue. Organic solvent extraction is widely used for isolating a broader range of compounds, including less polar molecules. Common solvents include ethanol, methanol, acetone, and ethyl acetate. The choice of solvent depends on the polarity of the target compounds. The plant material is typically macerated in the solvent for a specified period, followed by filtration and solvent evaporation to obtain the concentrated extract. Sequential extraction using solvents of increasing polarity can be employed to fractionate different groups of compounds. Supercritical fluid extraction, often using carbon dioxide, is a more advanced technique that offers advantages in terms of selectivity and purity. This method involves using CO2 in a supercritical state, which has properties of both a liquid and a gas, allowing it to penetrate plant material efficiently and dissolve specific compounds. The extracted compounds are then separated from the CO2 by depressurization. This method is particularly useful for extracting heat-sensitive compounds and producing solvent-free extracts. Steam distillation is commonly used for extracting volatile compounds such as essential oils. The plant material is exposed to steam, which causes the volatile compounds to vaporize. The vapor is then condensed and collected, with the oil separating from the water due to differences in density. Microwave-assisted extraction and ultrasound-assisted extraction are modem techniques that can enhance the efficiency and speed of extraction. These methods use microwave energy or ultrasonic waves to disrupt plant cell walls, facilitating the release of bioactive compounds. They can be combined with various solvents to improve yield and reduce extraction time. Enzyme-assisted extraction involves the use of specific enzymes to break down plant cell walls, increasing the yield of certain compounds. This method can be particularly effective for extracting polysaccharides and other complex molecules. After the initial extraction, further purification steps may be employed, such as liquid-liquid partitioning, column chromatography, or high-performance liquid chromatography (HPLC), to isolate specific compounds or groups of compounds. The choice of purification method depends on the chemical properties of the target compounds and the desired purity of the final extract. Throughout the extraction process, care must be taken to minimize degradation of sensitive compounds. This may involve working under nitrogen atmosphere, using low temperatures, or adding stabilizers. The final extract may be further processed into various forms such as powders, tinctures, or standardized extracts for use in pharmaceutical, nutraceutical, or cosmetic applications. Quality control measures, including chemical analysis and bioassays, are typically implemented to ensure consistency and efficacy of the extracts.

Plant extracts as a source for shikonin:

In some or all embodiments, plant A is of a Lithospermum genus. Lithospermum is a genus of flowering plants in the borage family, Boraginaceae, comprising approximately 50 to 60 species. Commonly referred to as gromwells or stoneseeds, species within this genus have been utilized in traditional medicine for various health benefits. For instance, Lithospermum officinale has been used historically as a female contraceptive in Europe, while Lithospermum erythrorhizon is recognized in Chinese herbal medicine for its antiviral properties, including inhibition of HIV- 1. Additionally, some species have demonstrated anti-inflammatory and antioxidant effects, contributing to cardiovascular health and overall well-being.

Known members of the Lithospermum genus include: Lithospermum affine, Lithospermum afromontanum, Lithospermum canescens, Lithospermum caroliniense, Lithospermum cinereum, Lithospermum diversifolium, Lithospermum erythrorhizon, Lithospermum flexuosum, Lithospermum hirsutum, Lithospermum incisum, Lithospermum inornatum, Lithospermum molle, Lithospermum officinale, Lithospermum papillosum, Lithospermum ruderale, Lithospermum scabrum, Lithospermum subsetosum. Gromwell is a preferred species in the context of the present invention. Preferably root extract of Lithospermum erythrorhizon and/or Lithospermum officinale, commonly known as common gromwell or European stoneseed, is a perennial plant native to Eurasia. Gromwell root extract is derived from the roots of the Lithospermum erythrorhizon plant. This extract is characterized by its rich content of naphthoquinone compounds, particularly shikonin, which contribute to its notable biological activities. These activities include anti-viral, anti-inflammatory, antimicrobial, and wound-healing properties, making it a valuable component in various therapeutic and cosmetic formulations. The extract is typically obtained through solvent extraction methods, ensuring the preservation of its bioactive constituents.

In some embodiments, gromwell may be replaced of supplemented with one or more representatives of the genus Lithospermum, which is part of the Boraginaceae family, commonly referred to as the borage or forget-me-not family. This family comprises approximately 2,000 species distributed across 100-130 genera, with a global presence in tropical, temperate, and arctic regions. Notable genera in this family include Borago (borage), Myosotis (forget-me-not), Pulmonaria (lungwort), Symphytum (comfrey), and Echium (viper's bugloss).

Natural products, such as plant extracts, present a unique challenge in formulation due to their inherent variability in active ingredient concentrations. This variability stems from factors including plant genetics, growing conditions, harvesting time, and extraction methods. When incorporating these natural extracts into compositions for pharmaceuticals, nutraceuticals, or cosmetics, one should account for these variations to ensure consistent potency and efficacy in the final product. The concentration of active ingredients in plant extracts can differ significantly between batches or sources, making it essential to adjust the amount of extract used based on its specific active content. This approach is necessary to maintain a standardized level of active materials in the composition, regardless of the natural variations in the raw materials. By addressing this variability, manufacturers can achieve precise formulations that meet quality standards and regulatory requirements, ensuring that consumers receive products with consistent and reliable effects across different production runs.

In some or all embodiments, the amount of the extract of plant A ranges 30-60 %wt of the total weight of the composition. Alternatively, the amount the extract of plant A ranges 30-50 %wt, 40-60 %wt, 30-40 %wt, or 50-60 %wt.

Alternatively, the amount of the extract of plant A is such that it accounts for an amount of shikonin that ranges 2-20 %wt of the total weight of the composition.

Plant extracts as a source for anthocyanin: In at least one embodiment of the present invention, plant B is selected from the Oryza genus, which comprises approximately 24 species of grasses, including both wild and cultivated varieties. Within this genus, several varieties exhibit high anthocyanin contents, making them particularly suitable for the purposes of this invention. Among these, black rice (Oryza sativa L.) represents a more preferred embodiment for the extract of plant B. Black rice, also known as purple rice or forbidden rice, is characterized by its distinctive dark color, which is attributed to its exceptionally high anthocyanin content. The anthocyanin pigments are primarily concentrated in the aleurone layer of the rice grain, giving it a deep purple to black appearance. The anthocyanin profile of black rice is dominated by cyanidin-3-glucoside and peonidin-3-glucoside, which are also known as TMPRSS2 and 3CL inhibitors, with smaller amounts of other anthocyanin derivatives. These compounds are responsible for the potent antioxidant properties of black rice and contribute significantly to its therapeutic potential. In addition to anthocyanins, black rice contains other beneficial compounds such as flavonoids, phenolic acids, y-oryzanol, and tocopherols, which further enhance its nutritional and medicinal value. The extraction process for obtaining the anthocyanin-rich fraction from black rice typically involves using acidified aqueous ethanol or methanol as solvents, followed by purification steps such as liquid-liquid partitioning or column chromatography. The resulting extract is characterized by its high anthocyanin content, typically ranging from 300 to 1000 mg per 100 g of rice, depending on the specific variety and extraction method used. This anthocyanin-rich extract from black rice demonstrates remarkable stability compared to anthocyanins from other sources, making it particularly suitable for incorporation into various formulations. The use of black rice extract in this invention leverages its potent antiviral, antioxidant, anti-inflammatory, and potential anti-cancer properties, which have been extensively documented in scientific literature. Furthermore, the choice of black rice as a source of anthocyanins aligns with the growing consumer preference for natural, plant-based ingredients in health and wellness products. It is worth noting that while black rice represents a preferred embodiment, other anthocyanin-rich varieties within the Oryza genus, such as red rice or certain wild rice species, may also be utilized in alternative embodiments of this invention, providing flexibility in sourcing and potentially offering unique phytochemical profiles that could be advantageous for specific applications.

In at least one embodiment, black rice may be replaced or supplemented with one or more representative of the variety known as Oryza sativa L. var. indica, which is a pigmented grain known for its deep purple-black color that is attributed to its high concentration of anthocyanins, a class of polyphenolic compounds with potent antioxidant properties. This rice variety is distinct from other types of rice due to its rich content of bioactive components, including flavonoids, phenolic acids, and vitamins, which contribute to its potential health benefits.

In at least one embodiment of the present invention, plant B is selected from the Aronia genus, which belongs to the Rosaceae family. The Aronia genus, commonly known as chokeberry, comprises several species known for their exceptionally high content of polyphenols, particularly anthocyanins. Among the species within this genus, Aronia melanocarpa, also known as black chokeberry, represents a more preferred embodiment for the extract of plant B due to its remarkably high anthocyanin content. The berries of Aronia melanocarpa are characterized by their astringent taste and exceptionally high levels of anthocyanins, proanthocyanidins, and other polyphenols. The anthocyanin content in black chokeberry is notably higher than in many other fruits, typically ranging from 400 to 2000 mg per 100 g of fresh berries, depending on the cultivar, growing conditions, and ripeness of the fruit. The primary anthocyanins found in black chokeberry are cyanidin-based, including cyanidin-3-galactoside, cyanidin-3-arabinoside, cyanidin-3- glucoside, and cyanidin-3-xyloside. These compounds are responsible for the deep purple -black color of the berries and contribute significantly to their potent antioxidant properties. In addition to anthocyanins, black chokeberry is rich in other phenolic compounds such as chlorogenic acid, neochlorogenic acid, and various quercetin derivatives, which further enhance its therapeutic potential. The extraction process for obtaining the anthocyanin-rich fraction from black chokeberry typically involves using acidified aqueous ethanol or methanol as solvents, followed by filtration and concentration steps. More advanced extraction methods, such as ultrasound- assisted extraction or supercritical fluid extraction, may be employed to improve yield and purity. The resulting extract is characterized by its high anthocyanin content and strong antioxidant capacity, making it particularly suitable for various applications in the fields of nutraceuticals, functional foods, and natural therapeutics. The use of black chokeberry extract in this invention leverages its well-documented health benefits, including potential cardiovascular protective effects, anti-inflammatory properties, and possible anti-cancer activities. Furthermore, the stability of Aronia anthocyanins during processing and storage is generally higher compared to anthocyanins from many other sources, which is advantageous for product formulation and shelflife. It is worth noting that while Aronia melanocarpa represents a preferred embodiment, other species within the Aronia genus, such as Aronia arbutifolia (red chokeberry) or Aronia prunifolia (purple chokeberry), may also be utilized in alternative embodiments of this invention. These species, while generally containing lower levels of anthocyanins compared to black chokeberry, may offer unique phytochemical profiles that could be beneficial for specific applications. The choice of black chokeberry as a source of anthocyanins aligns with the growing trend towards using natural, plant-based ingredients with strong scientific evidence supporting their health benefits.

In a least one embodiment, Oryza or Aronia genii may be replaced of supplemented with one or more representatives of the family Rosaceae, which is a diverse and economically important group of flowering plants comprising approximately 4,828 known species across 91 genera. This family encompasses a wide range of plants, including various trees, shrubs, and herbs, many of which produce edible fruits and are cultivated for ornamental purposes. Members of the Rosaceae family share certain characteristics, such as alternate leaves, presence of stipules, and flowers with five petals and numerous stamens. As alternatives to Black chokeberry, the Rosaceae family offers numerous species with similar attributes or potential uses. These include, but are not limited to, apples (Malus domestica), pears (Pyrus communis), cherries (Prunus avium), plums (Prunus domestica), strawberries (Fragaria x ananassa), raspberries (Rubus idaeus), blackberries (Rubus fruticosus), and roses (Rosa spp.). Each of these alternatives possesses unique qualities in terms of fruit production, ornamental value, or potential health benefits, making them suitable substitutes for Black chokeberry in various applications, such as food production, landscaping, or natural medicine.

In some or all embodiments, the amount of the extract of plant B ranges 30-60 %wt of the total weight of the composition. Alternatively, the amount the extract of plant B ranges 40-60 %wt, 30-50 %wt, 30-40 %wt, or 40-50 %wt.

Alternatively, the amount of the extract of plant B is such that it accounts for an amount of anthocyanins that ranges 15-50 %wt of the total weight of the composition.

Plant extracts as sources for flavonoids:

In some or all embodiments, the composition further includes an extract of plant C of a genus Scutellaria.

In some or all embodiments of the present invention, plant C is selected from the Scutellaria genus, which belongs to the Lamiaceae family and is commonly known as skullcap. The Scutellaria genus comprises approximately 350 species of flowering plants distributed worldwide, with many species traditionally used in various systems of medicine, particularly in East Asian countries. This genus is renowned for its rich flavonoid profile, which contributes significantly to its therapeutic potential. Among the species within this genus, Scutellaria baicalensis, also known as Chinese skullcap or Huang-qin, represents a more preferred embodiment for the extract of plant C due to its exceptionally high content of specific flavonoids, namely baicalin, baicalein, and wogonin. Scutellaria baicalensis is a perennial herb native to several East Asian countries and has been a staple of traditional Chinese medicine for centuries. The root of S. baicalensis is the primary source of bioactive compounds used in this invention. The flavonoid content in S. baicalensis roots can reach up to 25% of the dry weight, with baicalin often being the predominant compound. Baicalin, a flavone glycoside, is typically present in the highest concentration, followed by its aglycone form baicalein and another flavone called wogonin. These compounds are responsible for many of the plant's therapeutic effects and have demonstrated a wide range of biological activities, including potent antioxidant, anti-inflammatory, antiviral, and potential anti-cancer properties. The extraction process for obtaining the flavonoid-rich fraction from S. baicalensis typically involves using aqueous ethanol or methanol as solvents, sometimes with the addition of mild acids to enhance extraction efficiency. More advanced techniques such as ultrasound-assisted extraction or pressurized liquid extraction may be employed to improve yield and reduce processing time. The resulting extract is characterized by its high flavonoid content, particularly baicalin, baicalein, and wogonin, which can be quantified using high-performance liquid chromatography (HPLC) or other analytical methods. The use of S. baicalensis extract in this invention leverages its well-documented pharmacological activities, which may complement and potentially synergize with other components in the formulation. The stability of S. baicalensis flavonoids during processing and storage is generally good, which is advantageous for product formulation and shelf-life. It is worth noting that while S. baicalensis represents a preferred embodiment, other species within the Scutellaria genus, such as S. lateriflora (American skullcap) or S. barbata (Barbat skullcap), may also be utilized in alternative embodiments of this invention. These species, while generally containing lower levels of baicalin, baicalein, and wogonin compared to S. baicalensis, may offer unique phytochemical profiles that could be beneficial for specific applications. The choice of S. baicalensis as a source of flavonoids aligns with the growing interest in traditional medicinal plants and their potential applications in modern healthcare. Its inclusion in the formulation provides a rich source of specific flavonoids that may enhance the overall therapeutic efficacy of the invention through their antioxidant, anti-inflammatory, and other biological activities.

In some or all embodiments, the amount of the extract of plant C ranges 10-40 %wt of the total weight of the composition. Alternatively, the amount the extract of plant C ranges 20-40 %wt, 10-30 %wt, 20-30 %wt, or 30-40 %wt.

Alternatively, the amount of the extract of plant C is such that it accounts for an amount of baicalin and/or baicalein that ranges 5-30%wt of the total weight of the composition.

Plant extracts of genus Boswellia as sources for boswellic acids:

In some or all embodiments of the present invention, plant D is selected from the Boswellia genus, which belongs to the Burseraceae family and is commonly known as frankincense. The Boswellia genus comprises approximately 20 species of trees and shrubs native to the Arabian Peninsula, India, and parts of Africa. These species are renowned for their production of aromatic resins that have been used for millennia in traditional medicine, religious ceremonies, and perfumery. The genus is particularly notable for its high content of boswellic acids, a group of pentacyclic triterpene compounds that are responsible for many of the therapeutic properties associated with frankincense.

Among the species within this genus, Boswellia serrata, also known as Indian frankincense or Salai guggul, represents a more preferred embodiment for the extract of plant D due to its exceptionally high content of boswellic acids. Boswellia serrata is a moderate to large branching tree native to dry mountainous regions of India, Northern Africa, and the Middle East. The oleo- gum-resin obtained from the bark of B. serrata is the primary source of bioactive compounds used in this invention. This resin is rich in boswellic acids, particularly a-boswellic acid, P-boswellic acid, acetyl-P-boswellic acid, 11-keto-P-boswellic acid (KB A), acetyl- 11-keto-P-boswellic acid (AKBA), 3-O-acetyl-a-boswellic acid, 3-O-acetyl-P-boswellic acid, 3-O-acetyl-l l-keto-P- boswellic acid, lupeolic acid, 3-O-acetyl-lupeolic acid, incensole, and incensole acetate. These compounds have demonstrated potent anti-inflammatory, anti- arthritic, and potential anti-cancer properties. The boswellic acid content in B. serrata resin can range from 30% to 60% of the total resin weight, with AKBA often considered the most potent and therefore most studied of these compounds. The extraction process for obtaining the boswellic acid-rich fraction from B. serrata typically involves using organic solvents such as ethanol, methanol, or ethyl acetate, often followed by further purification steps. Advanced extraction techniques such as supercritical fluid extraction may also be employed to improve yield and purity. The resulting extract is characterized by its high boswellic acid content, which can be quantified using high-performance liquid chromatography (HPLC) or other analytical methods. The use of B . serrata extract in this invention leverages its well-documented anti-inflammatory and analgesic properties, which have been extensively studied in both in vitro and clinical settings. These properties are particularly beneficial for conditions such as osteoarthritis, rheumatoid arthritis, and other inflammatory disorders. Furthermore, recent research has suggested potential applications in the management of asthma, inflammatory bowel diseases, and certain types of cancer. It is worth noting that while B. serrata represents a preferred embodiment, other species within the Boswellia genus, such as Boswellia sacra (Sacred frankincense) Boswellia serrata, Boswellia papyrifera and Boswellia carteri or (Somali frankincense), may also be utilized in alternative embodiments of this invention. These species, while generally containing similar boswellic acid profiles, may offer unique compositional characteristics that could be advantageous for specific applications. The choice of B. serrata as a source of boswellic acids aligns with the growing interest in natural antiinflammatory agents and the potential for plant-based compounds to address chronic inflammatory conditions. Its inclusion in the formulation provides a potent source of boswellic acids that may enhance the overall therapeutic efficacy of the invention through their anti-inflammatory, analgesic, and potentially chemopreventive activities.

In some or all embodiments, the amount of the extract of plant D ranges 20-60 %wt of the total weight of the composition. Alternatively, the amount the extract of plant D ranges 30-50 %wt, 20-40 %wt, or 20-30 %wt.

Alternatively, the amount of the extract of plant D is such that it accounts for an amount of boswellic acids that ranges 30-50 %wt of the total weight of the composition.

A active ingredient-based composition:

While the use of plant extracts offers certain advantages, the utilization of isolated bioactive ingredients in this composition presents its own set of distinct benefits. This approach allows for precise control over the concentration and ratio of key compounds, namely shikonin and specific anthocyanins, enabling consistent and reproducible formulations across production batches. Such precision is particularly valuable in pharmaceutical applications where standardization is crucial. The use of isolated compounds facilitates more accurate dosing, which is essential for establishing clear dose-response relationships in clinical studies and optimizing therapeutic outcomes. Furthermore, this method allows for the elimination of potential interfering substances present in whole plant extracts, which may have undesired effects or interact unpredictably with other medications. The purity of isolated ingredients also simplifies the process of investigating specific molecular mechanisms of action, contributing to a deeper understanding of the composition's therapeutic effects. Additionally, the use of purified compounds can potentially enhance the potency of the formulation, allowing for lower overall dosages and potentially reducing the risk of side effects related to extraneous plant components. This approach also offers greater flexibility in formulation, allowing for precise adjustments to meet specific therapeutic needs or to create novel combinations not found in nature. Overall, the use of isolated bioactive ingredients provides a high degree of control and specificity, which can be particularly advantageous in certain research, development, and clinical applications.

In this aspect of the present invention, the composition is defined by its active ingredients, irrespective of whether these compounds are present in isolated form, or as components of plant extracts, or a combination thereof. According to an aspect of the present invention, there is provided a composition that act in synergy to improve health and fight infections, which includes at least the following active ingredients: a shikonin; and an anthocyanin.

Specifically, the composition comprises at least two key bioactive compounds: shikonin and an anthocyanin. The combination of shikonin and anthocyanins in this composition leverages the complementary and potentially synergistic effects of these compounds. Both exhibit antiinflammatory and antiviral properties through distinct yet potentially overlapping mechanisms, which may enhance the overall therapeutic efficacy of the composition. This molecular-level approach to defining the composition allows for precise control over the active ingredients, potentially leading to more consistent and predictable biological effects. The approach based on active ingredients allows for flexibility in sourcing these compounds while maintaining the desired therapeutic profile of the composition.

Shikonin:

Shikonin, chemically known as 5,8-dihydroxy-2-[(lS)-l-hydroxy-4-methylpent-3-en-l- yl] naphthalene- 1,4-dione, is a naphthoquinone derivative with a molecular formula of CieHieOs. This lipophilic compound is characterized by its deep red color and has a molecular weight of 288.3 g/mol. From a molecular perspective, shikonin's structure contributes to its diverse biological activities. The quinone moiety in shikonin is particularly important for its redox properties, which are believed to play a role in its anti-inflammatory and antiviral effects. Shikonin has demonstrated significant anti-inflammatory activity through various mechanisms, including the inhibition of pro-inflammatory cytokines such as TNF-a and IL-ip, and the suppression ofNF- KB signaling pathways. These actions contribute to its potential in treating inflammatory conditions. Moreover, shikonin exhibits potent antiviral properties against a range of viruses, including HIV, influenza, and herpes simplex virus. Its antiviral activity is thought to be mediated through multiple mechanisms, including direct virucidal effects and interference with viral replication processes.

Shikonin also exhibits senolytic activity by operating through a therapeutic mechanism that selectively targets and eliminates senescent cells within the body. These compounds exploit the unique vulnerabilities of senescent cells, which are characterized by their resistance to apoptosis and altered metabolic state. Shikonin, for instance, is believed to disrupt the anti-apoptotic pathways that senescent cells rely on for survival, particularly by inhibiting the BCL-2 family of proteins. This inhibition triggers programmed cell death specifically in senescent cells while leaving healthy cells largely unaffected. By removing these problematic senescent cells, shikonin and similar senolytic agents can potentially mitigate the deleterious effects associated with cellular senescence, such as chronic inflammation and tissue dysfunction. This targeted approach to eliminating senescent cells represents a promising strategy for addressing age-related diseases and potentially slowing the aging process itself, as the accumulation of senescent cells is a key hallmark of aging and age-related pathologies. In some or all embodiments, the amount of shikonin ranges 2-20 %wt of the total weight of the composition. Alternatively, the amount shikonin ranges 5-20 %wt, 10-20 %wt, 15-20 %wt, or 5-10 %wt.

Anthocyanin:

The anthocyanin component of the composition represents a class of water-soluble pigments belonging to the flavonoid family. Anthocyanins are characterized by their basic C6-C3- Ce carbon skeleton and are typically glycosylated in nature. The most common anthocyanidins (the aglycone form of anthocyanins) contemplated within the scope of the present invention, include without imitation, cyanidin, delphinidin, malvidin, pelargonidin, peonidin, and petunidin. These compounds vary in their hydroxylation and methoxylation patterns, which influence their color and bioactivity. From a molecular standpoint, anthocyanins possess strong antioxidant properties due to their ability to scavenge free radicals and chelate metal ions. This antioxidant activity contributes significantly to their anti-inflammatory effects. Anthocyanins have been shown to modulate inflammatory responses by inhibiting the production of pro-inflammatory mediators and enzymes such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Additionally, anthocyanins demonstrate antiviral properties against various pathogens. Their antiviral mechanisms include direct interaction with viral particles, inhibition of viral attachment and entry into host cells, and interference with viral replication processes. Some studies have shown that anthocyanins can inhibit the replication of influenza viruses and reduce the infectivity of herpes simplex virus.

In some or all embodiments, the amount of the anthocyanins in the composition ranges 15- 50 %wt of the total weight of the composition. Alternatively, the amount the anthocyanins ranges 30-50 %wt, 15-40 %wt, 40-50 %wt, or 15-30 %wt.

Flavonoids:

Flavonoids represent a diverse class of plant secondary metabolites that can be extracted and isolated from various plant sources. These compounds are characterized by their basic structure consisting of two phenyl rings and a heterocyclic ring, and are further classified into subgroups such as flavones, flavonols, flavanones, and isoflavones. Flavonoids are renowned for their wide range of biological activities, including antioxidant, anti-inflammatory, antiviral, and potential anti-cancer properties. The extraction of flavonoids typically involves the use of aqueous organic solvents such as ethanol or methanol, sometimes with the addition of mild acids to enhance extraction efficiency. Advanced techniques like ultrasound-assisted extraction or pressurized liquid extraction may be employed to improve yield and reduce processing time. The resulting extracts are characterized by their high flavonoid content, which can be quantified using analytical methods such as high-performance liquid chromatography (HPLC). Flavonoids generally exhibit good stability during processing and storage, making them advantageous for product formulation and shelf-life. The inclusion of flavonoid-rich extracts in formulations aligns with the growing interest in traditional medicinal plants and their potential applications in modern healthcare, providing a rich source of bioactive compounds that may enhance overall therapeutic efficacy through their various biological activities. Notable plant genera known for their high flavonoid content include Scutellaria, Camellia, Citrus, and Glycyrrhiza, among others.

Bosewelic acids:

Boswellic acids are a specific type of terpene compound. Terpenes are a large and diverse class of organic compounds produced by various plants, particularly conifers and other aromatic species. They are the primary constituents of essential oils and are characterized by their structure, which consists of multiple isoprene units. Boswellic acids, specifically, are pentacyclic triterpenes, meaning they are terpenoids composed of six isoprene units arranged in a specific five- ring structure. Found in the resin of Boswellia trees, particularly Boswellia serrata, these compounds share the basic carbon skeleton structure characteristic of terpenes. Like other terpenes, boswellic acids are synthesized in plants through the mevalonate pathway or the MEP (methylerythritol phosphate) pathway. They are classified as triterpenes, a subset of terpenes containing 30 carbon atoms. Similar to many terpenes, boswellic acids play a role in plant defense and have various biological activities that have made them interesting for potential medicinal applications. Their occurrence in specific plant species, primarily in the genus Boswellia, further exemplifies the diverse and complex structures that can arise from the basic terpene building blocks in nature.

Lipids and liposome building blocks:

The incorporation of lipids in the herein-disclosed compositions offers several advantages, particularly for orally-administered formulations thereof. Lipids can enhance the bioavailability of active ingredients, particularly those that are poorly water-soluble, by improving their solubility and facilitating absorption in the gastrointestinal tract. They can also provide a protective matrix for sensitive compounds, shielding them from degradation by stomach acid or enzymatic activity. Lipids can contribute to sustained release properties, allowing for a more prolonged and consistent delivery of active ingredients. Additionally, certain lipids may have beneficial effects on their own, such as improving gut health or providing essential fatty acids. The use of lipids can also enhance the palatability and mouthfeel of the composition, potentially improving patient compliance for oral medications.

Various types of lipids can assist in the protection and absorption of active ingredients. These include phospholipids, fatty acids, triglycerides, and cholesterol. Phospholipids, in particular, play a crucial role in the formation of liposomes, which are microscopic vesicles composed of one or more lipid bilayers. Liposomes can encapsulate both hydrophilic and hydrophobic compounds, protecting them from degradation and enhancing their absorption. The connection between liposomes and certain lipids is particularly important. Glycerophospholipids, sphingolipids, and sterols are key components in liposome formation due to their amphipathic nature, which allows them to self-assemble into bilayer structures in aqueous environments. These lipids can form the structural backbone of liposomes, with their hydrophilic heads facing the aqueous environment and hydrophobic tails forming the interior of the bilayer.

Specific glycerophospholipids and related compounds are contemplated within the scope of the present invention, such as phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol, phosphatidic acid, sphingomyelin, and cholesterol, possess an innate ability to form liposomes. This property stems from their molecular structure, which includes a hydrophilic head group and hydrophobic fatty acid tails. When dispersed in an aqueous medium, these molecules spontaneously arrange themselves into bilayer vesicles to minimize unfavorable interactions between their hydrophobic regions and water. The specific composition of these lipids can influence the properties of the resulting liposomes, including their size, stability, and ability to encapsulate different types of active ingredients. For instance, phosphatidylcholine is often used as a primary component in liposomal formulations due to its excellent bilayer-forming properties and biocompatibility.

Lecithin, a natural plant-based substance, is contemplated within the scope of the present invention as a source of many of the aforementioned lipids. Typically derived from soybeans, sunflower seeds, or egg yolks, lecithin is rich in phospholipids, particularly phosphatidylcholine. It also contains varying amounts of other phospholipids such as phosphatidylethanolamine and phosphatidylinositol. The composition of lecithin can vary depending on its source and extraction method, but it generally provides a complex mixture of lipids that are beneficial for liposome formation and other functions in oral formulations. Lecithin's natural origin and GRAS (Generally Recognized As Safe) status make it an attractive option for use in pharmaceutical and nutraceutical compositions. Its emulsifying properties can also contribute to improved stability and texture in oral formulations, while its phospholipid content supports the formation of liposomes for enhanced delivery of active ingredients.

In some or all embodiments, the amount of the lipid(s) in the composition ranges 10-40 %wt of the total weight of the composition. Alternatively, the amount lipid(s) ranges 10-20 %wt, 10-20 %wt, 20-40 %wt, or 30-40 %wt.

Additional and optional ingredients:

In some or all embodiments, all the compositions presented herein may further include at least one of the following isolated active ingredients: ivermectin; metformin;

2-acetoxybenzoic acid (aspirin); and

Nano-curcumin.

Ivermectin, a well-known antiparasitic agent, has demonstrated potential as a therapeutic agent in the context of viral infections. Recent studies have suggested that ivermectin may exhibit antiviral properties through multiple mechanisms. It has been proposed to inhibit the nuclear import of viral proteins, potentially interfering with viral replication. Additionally, ivermectin has shown anti-inflammatory effects, which could be beneficial in managing the inflammatory response associated with certain viral infections. Ivermectin is also a 3cl protease inhibitor, having IC50 of 40 micromolar. Some research has also indicated that ivermectin may have a role in modulating the host immune response, potentially enhancing antiviral immunity. While the exact mechanisms are still under investigation, the inclusion of ivermectin in this composition may contribute to its overall antiviral and anti-inflammatory efficacy.

In some or all embodiments, the amount of ivermectin in the composition ranges is less than 5 %wt of the total weight of the composition. Alternatively, the amount ivermectin ranges 1- 5 %wt, 2-4 %wt, or 1-2 %wt.

Metformin, primarily known for its use in diabetes management, has emerged as a potential therapeutic agent with diverse applications. In the context of this composition, metformin's inclusion is based on its demonstrated anti-inflammatory and potential antiviral properties. Metformin has been shown to inhibit the NF-KB signaling pathway, a key regulator of inflammatory responses. This anti-inflammatory action may be particularly beneficial in managing the inflammatory aspects of viral infections. Furthermore, some studies have suggested that metformin may have direct antiviral effects, although the mechanisms are not fully elucidated. Interestingly, metformin has also been associated with anti-aging effects, potentially through its activation of AMPK and inhibition of mTOR pathways. This anti-senescence activity could be particularly relevant in addressing age-related susceptibility to viral infections and their complications.

In some or all embodiments, the amount of metformin in the composition ranges up to 50 %wt of the total weight of the composition. Alternatively, the amount metformin ranges 10-50 %wt, 10-30 %wt, 5-20 %wt, or 20-40 %wt.

Aspirin, a widely used nonsteroidal anti-inflammatory drug (NSAID), is included in this composition for its well-established anti-inflammatory properties and potential antiviral effects. Aspirin's primary mechanism of action involves the inhibition of cyclooxygenase (COX) enzymes, which leads to reduced production of prostaglandins and thromboxanes, key mediators of inflammation. This anti-inflammatory action may be beneficial in managing the inflammatory response associated with viral infections. Additionally, some studies have suggested that aspirin may have direct antiviral effects, possibly through modulation of NF-KB signaling or other mechanisms. Aspirin's antiplatelet effects may also be relevant in addressing the coagulation abnormalities observed in some viral infections. Furthermore, recent research has indicated potential anti-senescence effects of aspirin, which could contribute to overall health and resilience against viral infections.

In some or all embodiments, the amount of aspirin in the composition ranges less than 30 %wt of the total weight of the composition. Alternatively, the amount aspirin ranges 10-30 %wt, 5-20 %wt, 5-10 %wt, or 20-30 %wt.

Curcumin, a natural polyphenol derived from turmeric, is included in this composition in its standard form or as nano-curcumin for enhanced bioavailability. Curcumin is renowned for its potent anti-inflammatory and antioxidant properties. In the context of viral infections, curcumin has demonstrated multiple beneficial effects. It has been shown to inhibit NF-KB activation, thereby reducing the production of pro-inflammatory cytokines. Curcumin has also exhibited direct antiviral activities against various viruses, potentially through interference with viral entry, replication, or assembly. Additionally, curcumin has shown promise as a natural protease inhibitor, which could be relevant in inhibiting both viral proteases and excessive activation of endogenous host proteases during infection. The anti-senescence properties of curcumin, mediated through various pathways including sirtuin activation and telomerase modulation, may contribute to cellular resilience and overall health.

The use of nano-curcumin formulations aims to overcome the limitations of curcumin's poor bioavailability, potentially enhancing its therapeutic efficacy in this composition. Nano- curcumin refers to a formulation of curcumin, the active compound derived from the turmeric root (Curcuma longa), that has been processed into nanoparticles, typically between 1-100 nanometers in size, to enhance its bioavailability and solubility. Curcumin is known for its potent antiinflammatory, antioxidant, and anticancer properties. The nano-formulation allows for improved absorption and therapeutic efficacy, making it suitable for various medical and nutritional applications. The production of nano-curcumin involves techniques such as nano-emulsification, encapsulation, or liposomal preparation to achieve the desired particle size, stability, and enhanced bioavailability. In some of all embodiments, the nano-curcumin ingredient is a liposomal formulations of nano-curcumin, which further enhances delivery by encapsulating the nanoparticles within phospholipid bilayers that protect the compound from degradation and facilitate targeted release.

A therapeutic mechanism-based composition:

In an aspect of the present invention, the composition is uniquely defined by the therapeutic mechanisms conferred by its ingredients, rather than solely by the specific compounds or plant extracts used. This approach acknowledges the complex and often multifaceted nature of biological interactions, where a single ingredient may contribute to multiple therapeutic mechanisms. By focusing on these mechanisms, the composition can be understood in terms of its functional properties and potential synergistic effects, rather than as a random mixture of compounds. It is important to note that while certain ingredients are associated with specific mechanisms, many act through multiple pathways, contributing to the overall efficacy of the composition in a comprehensive manner.

Thus, according to an aspect of the present invention, there is provided a composition that includes: a viral protease inhibitor; an endogenous host protease inhibitor; an anti-inflammatory agent; and an anti-senescence agent.

Viral protease inhibition is a key mechanism by which this composition exerts its therapeutic effects. The shikonin-rich extract, derived from plants such as Litho spermum erythrorhizon, has been associated with this mechanism. Shikonin has demonstrated the ability to inhibit viral proteases, which are crucial for viral replication. Additionally, certain isolated compounds in the composition, such as curcumin (or nano-curcumin), have shown potential as viral protease inhibitors. This mechanism is particularly relevant in the context of viral infections, where inhibition of viral proteases can significantly impair the virus's ability to replicate and spread. Endogenous host protease inhibition represents another important mechanism of action for this composition. Both the shikonin-rich extract and the anthocyanin-rich extract, which may be derived from various berries or other plant sources, have been associated with this mechanism. These plant extracts contain compounds that can modulate the activity of endogenous host proteases, which are often overactivated during respiratory infections and can contribute to tissue damage. Among the isolated compounds, curcumin has also demonstrated the ability to inhibit certain proteases, potentially contributing to this mechanism.

Anti-inflammatory activity is a crucial aspect of the composition's therapeutic profile. The anthocyanin-rich extract plays a significant role in this mechanism, with anthocyanins known for their potent anti-inflammatory properties. The shikonin-rich extract also contributes to this effect, as shikonin has demonstrated anti-inflammatory activities in various studies. Among the isolated compounds, aspirin, curcumin, and metformin are well-known for their anti-inflammatory properties. Ivermectin, while primarily known for other effects, has also shown some antiinflammatory potential. This multi-pronged approach to inflammation modulation allows the composition to address inflammatory processes through various pathways.

Anti- senescence activity represents an innovative aspect of this composition's therapeutic profile. Both the shikonin-rich and anthocyanin-rich extracts have been associated with anti-aging and cellular rejuvenation effects, which can be classified under anti-senescence activity. Among the isolated compounds, metformin has gained significant attention for its potential anti-aging effects, potentially through its influence on cellular energy metabolism. Curcumin has also demonstrated anti-senescence properties in various studies. This mechanism is particularly relevant in the context of age-related susceptibility to infections and the overall maintenance of cellular health and resilience.

Extracts from plants of the genus Scutellaria, particularly Scutellaria baicalensis (commonly known as Chinese skullcap), contribute significantly to the therapeutic profile of this composition. These extracts have been associated with multiple mechanisms of action, including viral protease inhibition, anti-inflammatory activity, and potential anti- senescence effects. The antiviral properties of Scutellaria extracts have been attributed to their ability to inhibit viral replication and entry into host cells. Their anti-inflammatory effects are well-documented, with studies showing modulation of various inflammatory pathways. Additionally, some research suggests that compounds found in Scutellaria extracts may have anti-aging properties, potentially contributing to the composition's anti- senescence activity.

Baicalin, baicalein, and wogonin, a group of flavonoids primarily found in Scutellaria species, are key active compounds contributing to multiple therapeutic mechanisms in this composition. These flavonoids have demonstrated significant antiviral properties, potentially through viral protease inhibition and interference with viral entry into host cells. They also exhibit potent anti-inflammatory effects, modulating various inflammatory pathways and cytokine production. Recent studies have suggested that these compounds may have anti-senescence properties, possibly through their antioxidant activities and effects on cellular signaling pathways involved in aging. The inclusion of these specific flavonoids enhances the composition's multifaceted approach to addressing viral infections and associated inflammatory responses.

Extracts from plants of the genus Boswellia, particularly Boswellia serrata, are included in this composition primarily for their potent anti-inflammatory properties. Boswellia extracts have been shown to inhibit 5-lipoxygenase, a key enzyme in the inflammatory cascade, as well as other inflammatory mediators. This mechanism of action contributes significantly to the overall antiinflammatory profile of the composition. While not as extensively studied for antiviral effects, some research suggests that Boswellia extracts may have mild antiviral properties. Additionally, the anti-inflammatory and antioxidant properties of Boswellia extracts may indirectly contribute to anti-senescence effects by reducing oxidative stress and chronic inflammation, both of which are associated with cellular aging.

Frankincense, a resin or an extract from plants of the genus Boswellia, contains several beneficial components that may contribute to human health. The most prominent are boswellic acids, which have anti-inflammatory properties and may help with conditions like arthritis, asthma, and inflammatory bowel diseases. Incensole and incensole acetate are compounds that might have neuroprotective effects and could potentially alleviate anxiety and depression. Terpenes found in frankincense, such as a-pinene and limonene, may have antimicrobial and analgesic properties. The resin also contains compounds like linalool, which might have calming effects. Some studies suggest that frankincense components may have anti-cancer properties, though more research is needed in this area. Additionally, frankincense contains antioxidants that could help protect cells from damage caused by free radicals. It's important to note that while these components show promise, more research is needed to fully understand their effects and optimal use in human health applications.

Frankincense is included in this composition for its diverse therapeutic properties. While primarily known for its anti-inflammatory effects, frankincense has also shown potential in other mechanisms relevant to this composition. Its anti-inflammatory activity is attributed to the inhibition of pro-inflammatory enzymes and the modulation of inflammatory mediators. Some studies have suggested that frankincense may have mild antiviral properties, although this mechanism is less established compared to its anti-inflammatory effects. Interestingly, recent research has indicated potential anti- senescence properties of boswellic acids, possibly related to its ability to protect against oxidative stress and DNA damage. These multiple mechanisms of action make frankincense a valuable component of the composition, contributing to its overall therapeutic profile in addressing viral infections and associated complications.

Viral protease inhibition:

The present invention encompasses compositions that target various viral proteases, which are crucial enzymes for viral replication and infectivity. These proteases play essential roles in the processing of viral polyproteins and the maturation of viral particles. By inhibiting these proteases, the compositions aim to disrupt the viral life cycle and potentially reduce the severity and duration of viral infections.

One of the key viral proteases targeted by the active ingredients in these compositions is the 3CL protease, also known as the main protease or Mpro. This protease is particularly important in the life cycle of coronaviruses, including SARS-CoV-2. Several compounds found in the compositions have demonstrated inhibitory activity against 3CL protease. These include baicalin and baicalein, flavonoids primarily derived from Scutellaria species, which have shown promising results in both in vitro and in silico studies. Quercetin, another flavonoid found in various plant sources, has also demonstrated 3CL protease inhibitory activity. Epigallocatechin gallate (EGCG), a polyphenol abundant in green tea, has been identified as a potential 3CL protease inhibitor through molecular docking studies and in vitro assays. Curcumin and its more bioavailable form, nano-curcumin, have shown inhibitory effects on 3CL protease, adding to their multi-faceted antiviral properties. Glycyrrhizin, a terpenoid compound found in licorice root, has also demonstrated potential as a 3CL protease inhibitor. Shikonin, a naphthoquinone derivative found in Lithospermum erythrorhizon and other plants, has shown promising results in inhibiting 3CL protease activity.

Beyond 3CL protease, the compositions may also target other viral proteases. For instance, some flavonoids like myricetin have shown inhibitory activity against proteases from different viral families. Polyphenols such as resveratrol have demonstrated broad-spectrum antiviral activity, potentially including protease inhibition. Stilbenoids like pterostilbene, hopeaphenol, and trans-s-viniferin, while less studied in the context of viral proteases, may contribute to the overall antiviral effects of the compositions.

Lignans such as arctigenin, sesamin, and podophyllotoxin have shown various antiviral properties, which may include protease inhibition. Alkaloids like berberine, camptothecin, and sanguinarine have demonstrated antiviral effects against multiple viruses, potentially through various mechanisms including protease inhibition. Terpenoids such as andrographolide and betulinic acid have shown broad- spectrum antiviral activity, which may involve protease inhibition among other mechanisms.

Quinones like tanshinone IIA and emodin, in addition to the aforementioned shikonin, have demonstrated antiviral properties that may include protease inhibition. Coumarins such as esculetin, psoralen, and scopoletin, while primarily known for other biological activities, may contribute to the overall antiviral effects of the compositions. Chaicones like xanthohumol, licochalcone A, and isoliquiritigenin have shown promising antiviral activities in various studies, potentially including protease inhibition.

Tannins such as punicalagin, chebulagic acid, and ellagic acid have demonstrated broadspectrum antiviral activities, which may involve protease inhibition among other mechanisms. Saponins like ginsenoside Rg3, saikosaponin D, and astragaloside IV have shown antiviral properties against various viruses, potentially through multiple mechanisms including protease inhibition.

While carotenoids such as lutein, lycopene, and P-carotene are primarily known for their antioxidant properties, they may contribute to the overall antiviral effects of the compositions. Anthocyanins like cyanidin, delphinidin, and malvidin have shown antiviral properties in various studies, which may include protease inhibition among other mechanisms.

Sulfur-containing compounds such as allicin, sulforaphane, and S-allyl cysteine, found in plants like garlic and cruciferous vegetables, have demonstrated antiviral properties that may involve protease inhibition. Lastly, peptide-based inhibitors like cyclotide, lunasin, and sunflower trypsin inhibitor represent a class of compounds that can directly interact with viral proteases, potentially offering highly specific inhibitory effects.

The diverse range of compounds included in these compositions allows for a multi-targeted approach to viral protease inhibition, potentially enhancing their overall antiviral efficacy and reducing the likelihood of viral resistance development.

In some or all embodiments, the targeted viral protease is 3CL protease, and the viral protease inhibitor is an anthocyanin and/or shikonin.

Endogenous host protease inhibition:

The present invention encompasses compositions that target various endogenous host proteases, which play crucial roles in both normal host physiology and pathological conditions. During certain disease states, particularly viral infections, these proteases can become dysregulated, leading to excessive tissue damage and inflammation. By modulating the activity of these proteases, the compositions aim to maintain lung homeostasis and potentially reduce the severity of respiratory complications associated with viral infections. Cysteine proteases are a key group of enzymes targeted by several components of these compositions. Shikonin, tanshinone IIA, and betulinic acid have demonstrated inhibitory effects on cysteine proteases, potentially contributing to lung tissue protection. These compounds, derived from various plant sources, may help modulate the activity of cathepsins and other cysteine proteases involved in lung inflammation and tissue remodeling.

Flavonoids play a significant role in the protease-modulating effects of these compositions. Quercetin, kaempferol, baicalin, and baicalein have shown inhibitory activities against various proteases, including those implicated in lung pathologies. These compounds may help regulate the balance of proteolytic activity in the lungs, potentially reducing excessive tissue breakdown during inflammatory conditions.

Polyphenols such as epigallocatechin gallate (EGCG), curcumin (and its more bioavailable form, nano-curcumin), and resveratrol are included for their broad-spectrum protease inhibitory activities. These compounds have demonstrated the ability to inhibit multiple classes of proteases, including serine proteases and matrix metalloproteinases (MMPs), which are crucial in lung tissue remodeling and inflammatory processes.

Stilbenoids like pterostilbene, hopeaphenol, and trans-s-viniferin, while less studied in the context of host proteases, may contribute to the overall protective effects of the compositions through their antioxidant and anti-inflammatory properties. Lignans such as arctigenin, sesamin, and podophyllotoxin have shown various biological activities that may indirectly modulate protease activity in the lungs.

Alkaloids including berberine, chelerythrine, and sanguinarine have demonstrated protease inhibitory activities in various studies. These compounds may help regulate the activity of proteases involved in lung inflammation and tissue damage. Terpenoids, particularly boswellic acids found in frankincense, glycyrrhizin from licorice, and andrographolide, have shown promising effects in modulating protease activity. Boswellic acids, in particular, have demonstrated potent inhibitory effects on elastase, a key protease involved in lung tissue destruction.

Quinones like shikonin, tanshinone IIA, and emodin exhibit multi-faceted biological activities, including protease inhibition. These compounds may help regulate the activity of various host proteases, contributing to tissue protection and anti-inflammatory effects. Coumarins such as esculetin, psoralen, and scopoletin, while primarily known for other biological activities, may contribute to the overall protease-modulating effects of the compositions.

Chaicones like xanthohumol, licochalcone A, and isoliquiritigenin have shown promising protease inhibitory activities in various studies. These compounds may help regulate the activity of proteases involved in lung inflammation and tissue remodeling. Tannins such as punicalagin, chebulagic acid, and ellagic acid have demonstrated broad- spectrum protease inhibitory activities, which may be beneficial in maintaining lung tissue integrity.

Saponins like ginsenoside Rg3, saikosaponin D, and astragaloside IV have shown various biological activities that may include protease modulation. While carotenoids such as lutein, lycopene, and P-carotene are primarily known for their antioxidant properties, they may indirectly contribute to protease regulation by reducing oxidative stress in lung tissues.

Anthocyanins like cyanidin, delphinidin, and malvidin have shown anti-inflammatory and antioxidant properties that may indirectly modulate protease activity in the lungs. Sulfur- containing compounds such as allicin, sulforaphane, and S-allyl cysteine, found in plants like garlic and cruciferous vegetables, have demonstrated various biological activities that may include protease modulation.

Peptide-based inhibitors like cyclotide, lunasin, and sunflower trypsin inhibitor represent a class of compounds that can directly interact with proteases, potentially offering highly specific inhibitory effects on host proteases. These natural peptides may provide targeted modulation of protease activity in the lungs.

The compositions also include specific inhibitors for different classes of proteases. Serine protease inhibitors such as boswellic acid, glycyrrhizin, and EGCG may help regulate the activity of proteases like neutrophil elastase and trypsin. Matrix metalloproteinase (MMP) inhibitors, including curcumin/nano-curcumin, resveratrol, and baicalein, may help modulate tissue remodeling processes in the lungs. Elastase inhibitors, particularly boswellic acids from frankincense, as well as flavonoids like quercetin and kaempferol, may help protect lung tissue from excessive degradation by neutrophil elastase.

The diverse range of compounds included in these compositions allows for a multi-targeted approach to endogenous host protease modulation. This comprehensive strategy aims to maintain a balance of proteolytic activity in the lungs, potentially reducing tissue damage and inflammation associated with respiratory infections and other lung pathologies.

In some embodiments, the endogenous host protease is transmembrane serine protease 5, and the endogenous host protease inhibitor is an anthocyanin, a boswellic acid and/or shikonin.

Anti-inflammatory effect:

The present invention encompasses compositions that provide significant antiinflammatory activity through a diverse array of active ingredients. This multi-faceted approach to inflammation modulation allows for comprehensive management of inflammatory processes associated with various conditions, including viral infections and respiratory disorders. Flavonoids play a crucial role in the anti-inflammatory properties of these compositions. Compounds such as quercetin, kaempferol, baicalin, and baicalein have demonstrated potent antiinflammatory effects through various mechanisms, including inhibition of pro-inflammatory enzymes and modulation of cytokine production. These flavonoids can help mitigate excessive inflammatory responses and potentially reduce tissue damage associated with inflammation.

Polyphenols, including epigallocatechin gallate (EGCG), resveratrol, and curcumin, contribute significantly to the anti-inflammatory profile of the compositions. These compounds have shown broad-spectrum anti-inflammatory activities, including inhibition of nuclear factorkappa B (NF-KB) signaling, modulation of inflammatory cytokines, and reduction of oxidative stress. Curcumin, in particular, has demonstrated potent anti-inflammatory effects and is included in both standard and nano-formulations to enhance bioavailability.

Stilbenoids such as pterostilbene, hopeaphenol, and trans-s-viniferin offer additional antiinflammatory benefits. These compounds have shown the ability to modulate inflammatory pathways and reduce oxidative stress, contributing to the overall anti-inflammatory effects of the compositions. Lignans like arctigenin, sesamin, and podophyllotoxin have demonstrated various anti-inflammatory properties in different studies, adding to the diverse array of anti-inflammatory agents in the compositions.

Alkaloids, including berberine, chelerythrine, and sanguinarine, contribute to the antiinflammatory profile through various mechanisms, including modulation of inflammatory mediators and signaling pathways. Terpenoids, particularly frankincense resin and its active components boswellic acids, as well as andrographolide, have shown potent anti-inflammatory effects. Boswellic acids, for instance, are known inhibitors of 5-lipoxygenase, a key enzyme in the inflammatory cascade.

Quinones such as shikonin, tanshinone IIA, and emodin exhibit multi-faceted antiinflammatory activities, including inhibition of pro-inflammatory cytokines and modulation of inflammatory signaling pathways. Coumarins like esculetin, psoralen, and scopoletin, while less studied for their anti-inflammatory effects, may contribute to the overall anti-inflammatory profile of the compositions.

Chaicones, including xanthohumol, licochalcone A, and isoliquiritigenin, have demonstrated significant anti-inflammatory properties in various studies. These compounds can modulate inflammatory pathways and reduce the production of pro-inflammatory mediators. Tannins such as punicalagin, chebulagic acid, and ellagic acid offer potent anti-inflammatory and antioxidant effects, contributing to the overall anti-inflammatory activity of the compositions. Saponins like ginsenoside Rg3, saikosaponin D, and astragaloside IV have shown various anti-inflammatory properties, including modulation of inflammatory cytokines and signaling pathways. Carotenoids such as lutein, lycopene, and P-carotene, while primarily known for their antioxidant properties, can indirectly contribute to anti-inflammatory effects by reducing oxidative stress.

Anthocyanins, including cyanidin, delphinidin, and malvidin, offer both direct antiinflammatory effects and indirect benefits through their potent antioxidant properties. Sulfur- containing compounds such as allicin, sulforaphane, and S-allyl cysteine, found in plants like garlic and cruciferous vegetables, have demonstrated various anti-inflammatory activities, including modulation of inflammatory mediators and antioxidant effects.

Peptide-based anti-inflammatory agents like cyclotide, lunasin, and sunflower trypsin inhibitor represent a class of compounds that can directly modulate inflammatory processes, offering potential for highly specific anti-inflammatory effects.

The compositions also include specific inhibitors of key inflammatory pathways. Nuclear factor-kappa B (NF-KB) inhibitors such as boswellic acids from frankincense, curcumin, and andrographolide can help regulate this central mediator of inflammation. Cytokine modulators like quercetin, resveratrol, and baicalein can help balance the production and activity of various inflammatory cytokines.

Inflammasome inhibitors, including curcumin/nano-curcumin, epigallocatechin gallate (EGCG), and tanshinone IIA, target a crucial component of the innate immune response, potentially reducing excessive inflammatory activation. Cyclooxygenase (COX) inhibitors such as nano-curcumin, boswellic acids, and licochalcone A can help modulate prostaglandin production, a key aspect of the inflammatory response.

Lipoxygenase (LOX) inhibitors, including anthocyanins, luteolin, and myricetin, target another important pathway in the inflammatory cascade, potentially reducing the production of pro-inflammatory leukotrienes.

The diverse range of anti-inflammatory compounds included in these compositions allows for a comprehensive approach to inflammation modulation. This multi-targeted strategy aims to address various aspects of the inflammatory response, potentially offering more effective and balanced anti-inflammatory effects compared to single-compound approaches.

In some embodiments the anti-inflammatory agent in the composition is an anthocyanin, a boswellic acid such as incensole and incensole acetate, and/or curcumin/nano-curcumin.

Anti-senescence effect: The present invention encompasses compositions that provide significant anti-senescence activity through a diverse array of active ingredients. This multi-faceted approach to combating cellular aging and promoting longevity allows for comprehensive management of age-related processes, potentially enhancing overall health and resilience against various age-associated conditions, including increased susceptibility to viral infections.

Telomerase activators play a crucial role in the anti-senescence properties of these compositions. Compounds such as cycloastragenol, astragaloside IV, and Telomerase Activator 2 (TAT2) have demonstrated the ability to enhance telomerase activity, potentially slowing down cellular aging by maintaining telomere length. These agents may help preserve cellular function and replicative capacity, particularly in immune cells, which is crucial for maintaining a robust immune response.

Senolytic agents, including quercetin, fisetin, and piperlongumine, contribute to the antisenescence profile by selectively eliminating senescent cells. These compounds can help reduce the accumulation of dysfunctional cells that contribute to age-related inflammation and tissue dysfunction, potentially improving overall tissue health and function. mTOR inhibitors such as metformin, rapamycin (sirolimus), everolimus, and resveratrol offer another mechanism for promoting longevity and cellular health. By modulating the mTOR pathway, these compounds can influence cellular metabolism, protein synthesis, and autophagy, potentially mimicking some of the beneficial effects of caloric restriction on lifespan and healthspan.

NAD+ boosters, including nicotinamide riboside, nicotinamide mononucleotide (NMN), and niacin (vitamin B3), are included to support cellular energy metabolism and DNA repair processes. By enhancing NAD+ levels, these compounds can potentially improve mitochondrial function and activate sirtuins, key regulators of cellular health and longevity.

Sirtuin activators such as resveratrol, pterostilbene, and fisetin complement the NAD+ boosters by directly activating sirtuin enzymes. These compounds can influence various cellular processes, including gene expression, metabolism, and stress resistance, potentially contributing to improved cellular health and longevity.

Antioxidants and free radical scavengers, including vitamin C, vitamin E, and coenzyme Q10, are incorporated to combat oxidative stress, a key contributor to cellular aging. These compounds can help protect cellular components from oxidative damage, potentially preserving cellular function and reducing age-related deterioration.

DNA repair enhancers such as shikonin, nicotinamide, Oxoguanine Glycosylase 1 (OGGI) activators, and Poly (ADP-ribose) Polymerase inhibitors (PARP inhibitors) are included to support genomic stability. By enhancing the cell's ability to repair DNA damage, these compounds may help maintain cellular integrity and function, potentially slowing down age-related decline.

Autophagy inducers like spermidine, curcumin/nano-curcumin, and urolithin A promote cellular "housekeeping" processes. By enhancing the removal of damaged cellular components, these compounds can help maintain cellular health and function, potentially contributing to longevity.

Mitochondrial function enhancers such as pyrroloquinoline quinone (PQQ), Mitoquinone (MitoQ), and SS-31 (elamipretide) target cellular energy production. By improving mitochondrial health and efficiency, these compounds can potentially enhance overall cellular function and resilience against age-related decline.

Epigenetic modulators including valproic acid, sodium butyrate, and epigallocatechin gallate (EGCG) offer the potential to influence gene expression patterns associated with aging. These compounds may help maintain a more youthful epigenetic profile, potentially influencing various aspects of cellular function and longevity.

Stem cell activators such as SB203580 (p38 Mitogen-Activated Protein Kinase inhibitor), Y-27632 (Rho-associated protein kinase inhibitor), and fucoidan are included to support tissue regeneration and maintenance. By enhancing stem cell function, these compounds may contribute to improved tissue repair and homeostasis.

Inflammasome inhibitors like MCC950, OLT1177, and tranilast target age-related inflammation. By modulating inflammasome activity, these compounds can potentially reduce chronic low-grade inflammation associated with aging, contributing to overall cellular and tissue health.

Senescence-associated secretory phenotype (SASP) inhibitors such as glucocorticoids, Janus Kinase inhibitors (JAK inhibitors) (ruxolitinib, tofacitinib), and apigenin are incorporated to modulate the inflammatory and tissue-degrading factors secreted by senescent cells. By reducing the negative impact of the SASP, these compounds may help maintain tissue function and reduce age-related inflammation.

Proteostasis regulators including 17- Allylamino- 17-demethoxygeldanamycin (17-AAG, tanespimycin), 17-Demethoxy-17-allylamino-geldanamycin (17-DMAG, alvespimycin), and arimoclomol support proper protein folding and degradation. By maintaining proteostasis, these compounds can potentially reduce the accumulation of misfolded proteins associated with cellular aging and age-related diseases.

Cellular reprogramming factors such as octamer-binding transcription factor 4 (Oct4), sexdetermining region Y-box 2 (Sox2), and Kruppel-like factor 4 (Klf4) offer the potential to rejuvenate cellular function. While the use of these factors requires careful control, they represent a cutting-edge approach to cellular rejuvenation.

Hormone replacements/modulators including growth hormone, dehydroepiandrosterone (DHEA), and melatonin are included to address age-related hormonal changes. These compounds may help maintain various physiological functions that decline with age, potentially contributing to overall health and longevity.

Extracellular matrix (ECM) modulators such as hyaluronic acid, collagen peptides, and glucosamine support tissue structure and function. By maintaining ECM integrity, these compounds can potentially contribute to tissue health and function, particularly in connective tissues.

Caloric restriction mimetics like 2-deoxyglucose, hydroxycitrate, and spermidine aim to replicate some of the beneficial effects of caloric restriction on lifespan and healthspan. These compounds can potentially influence cellular metabolism and stress resistance pathways associated with longevity.

Exercise mimetics such as 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR), GW501516, and SR9009 are included to potentially replicate some of the beneficial effects of physical exercise on cellular health and metabolism. These compounds may contribute to improved metabolic health and cellular function.

Genomic stability enhancers including nuclear receptor binding to intronic DNA (NR- BID), LB-100 (Protein Phosphatase 2A inhibitor, PP2A inhibitor), and anthocyanins support the maintenance of genomic integrity. By enhancing the cell's ability to maintain its genetic material, these compounds may contribute to cellular longevity and function.

The diverse range of anti- senescence compounds included in these compositions allows for a comprehensive approach to combating cellular aging. This multi-targeted strategy aims to address various aspects of the aging process, potentially offering more effective and balanced antisenescence effects compared to single-compound approaches. By targeting multiple pathways and mechanisms involved in cellular aging, these compositions aim to enhance overall cellular health, resilience, and longevity, potentially contributing to improved health outcomes and resistance to age-related conditions.

In some embodiments, the anti- senescence agent is shikonin, metformin and/or an anthocyanin.

Source-Ingredient-Activity correlation:

The invention provided herein is defined under three categories, source (plant extracts), active ingredient, and therapeutic activity /mechanism. The plant category comprises four types of plant extracts, A, B C and D; the active ingredient category comprises four groups, shikonin, anthocyanin, flavonoid and boswellic acid; and activity/mechanism category comprises four groups, viral protease inhibition, endogenous host protease inhibition, anti-inflammatory effect and anti- senescence effect. Each of these categories is further supplemented with a class of isolated active ingredients which may be naturally occurring and/or synthetic, and further supplemented with lipids.

Table 1 below presents a non-limiting list of active ingredients along- side with their plant or otherwise source, the activity mechanism associated therewith, and other information.

Table 1

Baicalin sourced from Scutellaria baicalensis, demonstrates potent antiviral activity by inhibiting SARS-CoV-2 3CL protease, TMPRSS2, and papain-like protease, with extensive in vitro evidence supporting these mechanisms. Its anti-inflammatory properties include suppression of the NF-KB pathway and inhibition of cytokine storm mediators, which are well-documented in scientific literature. Baicalin demonstrates preferential distribution to lung tissue in animal studies, optimizing its action against respiratory viral infections. Recent research confirms it directly reduces viral RNA synthesis, making it a particularly promising agent for respiratory viral infections.

Baicalein, also from Scutellaria baicalensis, directly targets viral replication by inhibiting RNA-dependent RNA polymerase and 3CL protease enzymes, with both in silico and in vitro evidence supporting these mechanisms. It modulates JAK-STAT inflammatory pathways and attenuates viral-induced inflammation in respiratory tissues, helping prevent excessive tissue damage during infection. The compound demonstrates superior plasma stability compared to its glycosylated derivative baicalin, enhancing its systemic bioavailability. This improved pharmacokinetic profile makes baicalein particularly valuable for systemic antiviral applications.

Anthocyanins from Oryza sativa (Black Rice) display significant anti-inflammatory and antioxidant properties by inhibiting NF-KB pathways and NLRP3 inflammasome activation, effects that are well-established in scientific literature. They provide senomorphic activity via AMPK and SIRT1 activation, helping restore cellular function in stressed cells during viral infections. Their bioavailability is enhanced when consumed with small amounts of dietary fat, which facilitates absorption through improved micelle formation in the intestine. Fermentation processes can further increase bioavailability of bound phenolics, making fermented black rice products potentially more effective.

Phosphatidylserine acts as a cell membrane modulator that may inhibit viral fusion with host cells and modulate ACE2 receptor interactions, although direct antiviral activity remains an active area of research. It facilitates immune system regulation, enhances phagocytosis of viral particles, and supports apoptotic cell clearance — roles that are well-documented scientifically. Its amphipathic structure allows for efficient incorporation into cell membranes, while liposomal formulations enhance bioavailability by protecting the phospholipid from degradation in the digestive tract. Phosphatidylserine supports membrane repair and cellular recovery following viral-induced injury, making it valuable for tissue recovery.

Gromwell extract contains naphthoquinone derivatives like shikonin that target RNA- dependent RNA polymerase, effectively inhibiting viral replication machinery. Its antiinflammatory properties reduce tissue damage during infection by suppressing pro-inflammatory mediators, effects observed in multiple preclinical studies. The extract provides comprehensive protection through multiple bioactive constituents working synergistically, with the natural matrix enhancing bioavailability compared to isolated compounds. These synergistic effects highlight the advantage of whole-plant extracts over isolated compounds for complex viral infections.

Shikonin demonstrates powerful antiviral activity by inhibiting SARS-CoV-2 main protease through a unique binding mode specifically targeting the catalytic dyad (His41-Cysl45), as shown in binding studies. It suppresses IL-6 and STAT3-mediated inflammatory pathways that contribute to cytokine storm, mechanisms supported by extensive research. Its lipophilic nature facilitates cellular penetration, though bioavailability can be enhanced through lipid-based delivery systems. Shikonin's dual mechanism targeting both viral replication and inflammatory responses provides comprehensive protection against respiratory viral infections.

Anthocyanins from Vaccinium myrtillus (Bilberry) specifically inhibit viral attachment to host cells by competing for ACE2 binding sites and interfering with viral neuraminidase, as demonstrated in computational models and in vitro studies. They modulate MAPK inflammatory pathways and reduce HMGB 1 -driven inflammation, mechanisms consistent with their polyphenolic structure. By activating Nrf2 antioxidant pathways, bilberry anthocyanins protect infected tissues from oxidative stress and support vascular integrity. Standardized extracts with verified anthocyanin content demonstrate optimal bioavailability and consistent therapeutic effects.

Anthocyanins from Aronia melanocarpa (Chokeberry) inhibit viral hemagglutinin and viral attachment to host cells, with demonstrated activity against influenza virus. They modulate NF-KB, IL-6, and STAT3 inflammatory pathways while promoting anti-senescence mechanisms through SIRT1 activation. Aronia anthocyanins specifically reduce vascular inflammation, protecting against virus-associated vascular complications seen in severe infections. Bioavailability is enhanced through formulation with vitamin C, which stabilizes these compounds and extends their half-life.

Chrysanthemin (Cyanidin 3-glucoside) inhibits viral proteases including 3CLpro and PLpro based on in silico binding studies, while modulating the PI3K/Akt inflammatory pathway. It provides antipyretic effects useful for managing fever during viral infections, consistent with traditional medicinal applications. The glycoside moiety improves initial solubility and absorption, though intestinal P-glucosidases cleave the sugar portion, affecting bioavailability of the aglycone. This compound's anti-inflammatory and membrane-stabilizing properties help protect cellular integrity during viral infections. Chrysanthemum extract contains flavonoids and sesquiterpene lactones that inhibit HMGB 1 and TLR4 inflammatory mediators, as observed in preclinical studies. It suppresses PGE2 synthesis, reducing inflammation-associated symptoms like fever and pain, effects that support its traditional use for fever and inflammation. The diverse phytochemical profile creates synergistic effects that enhance overall therapeutic efficacy beyond what individual constituents would provide. These multi-target effects make chrysanthemum extract particularly valuable for managing the complex symptomatology of viral infections. Chrysanthemum also inhibit the host protease which is a target both for corona and influenza viruses named TMPRSS2.

Cyanidin demonstrates direct antiviral activity by inhibiting 3CLpro and TMPRSS2 viral entry mechanisms in computational and in vitro studies. It suppresses JNK/p38 MAPK inflammatory signaling pathways that contribute to tissue damage, mechanisms consistent with its polyphenolic structure. Bioavailability is limited by extensive phase II metabolism (glucuronidation, sulfation), though consumption with organic acids can enhance absorption. Cyanidin's potent antioxidant capacity helps preserve cellular function during infection, providing additional protection beyond direct antiviral effects.

BanLanGen (Isatis tinctoria root) induces Type I interferons, enhancing innate antiviral immune responses based on traditional usage and modem research. It inhibits viral neuraminidase, blocking influenza and other respiratory vims replication, as demonstrated in multiple studies. BanLanGen modulates the JAK-STAT pathway to balance immune responses, preventing both viral replication and excessive inflammation. Traditional water decoctions maximize extraction of water-soluble alkaloids and glucosinolates that contribute to its antiviral activity.

Quercetin functions as a zinc ionophore that enhances cellular antiviral defenses by facilitating zinc entry into cells while directly inhibiting viral proteases, mechanisms supported by multiple in vitro studies. It demonstrates senolytic or anti-senescence effects through PI3K/Akt/mT0R pathway inhibition, particularly when combined with other agents like dasatinib. Its naturally low bioavailability (5-10%) is significantly enhanced when formulated with phospholipids or administered with piperine, making combination therapy particularly effective. Quercetin's comprehensive anti-inflammatory profile includes inhibition of NF-KB signaling and reduction of pro-inflammatory cytokines, providing multi-target benefits.

Metformin activates AMPK and inhibits mTOR signaling, providing both antiviral and senomorphic effects that are well-documented in scientific literature. It modulates cellular metabolism to create an unfavorable environment for viral replication, while reducing inflammatory responses. Its hydrophilic nature requires active transport via organic cation transporters, with maximum bioavailability achieved through extended-release formulations. Metformin helps preserve mitochondrial function during viral infection, supporting tissue recovery and cellular energy production.

Ivermectin inhibits importin a/pi -mediated nuclear transport required for viral replication and may block viral helicase activity, although clinical antiviral efficacy remains controversial. It demonstrates PAK1 inhibition, which reduces inflammatory signaling cascades activated during viral infection. Bioavailability is enhanced when taken with high-fat meals, though its large molecular size limits crossing the blood-brain barrier. Ivermectin's immunomodulatory effects help prevent excessive immune responses while maintaining antiviral activity in preclinical models.

Fisetin exhibits senolytic properties by clearing senescent cells through PI3K/Akt/mT0R inhibition, with significant evidence from animal models. It directly inhibits viral 3CLpro in computational studies while suppressing inflammatory mediators IL-6 and TNF-a. Its bioavailability is relatively low due to extensive first-pass metabolism, but can be enhanced through lipid-based formulations or co-administration with piperine. Fisetin provides triple action benefits — antiviral, anti-inflammatory, and senolytic — that support tissue repair after infection.

Artemisinin blocks SARS-CoV-2 endocytosis according to preliminary studies and inhibits NF-KB inflammatory signaling pathways. Its unique endoperoxide structure generates reactive oxygen species in the presence of heme, effectively targeting viral components and infected cells. Poor water solubility limits absorption; however, semi-synthetic derivatives with improved pharmacokinetic profiles like artesunate are available. Artemisinin induces heme- mediated oxidative stress selectively in infected cells, providing targeted antiviral activity with potentially reduced side effects.

Aspirin inhibits cyclooxygenase enzymes and NF-KB inflammatory pathways activated during viral infections, with effects on NLRP3 inflammasome observed at higher doses. It suppresses NLRP3 inflammasome activation that contributes to cytokine storm in severe viral infections. Aspirin's anticoagulant (antiplatelet) properties help prevent thrombotic complications associated with severe viral infections — a well-established clinical benefit. Enteric-coated formulations improve gastrointestinal tolerance while maintaining therapeutic efficacy through systemic absorption.

Fucoidan from seaweeds competitively inhibits viral attachment to host cells by binding to the same receptors used for viral entry, utilizing its multivalent structure. It modulates p38 MAPK/AP-1 inflammatory pathways to reduce tissue damage during infection, effects consistent with its polysaccharide structure. Molecular weight is a critical factor in its bioactivity, with medium molecular weight fractions (20-50 kDa) demonstrating optimal antiviral activity through stronger receptor binding. Oral bioavailability remains limited due to its large molecular size, a common challenge with complex polysaccharides.

Aloe Vera Extract inhibits viral entry while modulating TLR4-mediated inflammatory responses, with its acemannan component specifically activating macrophages while maintaining anti-inflammatory balance. It enhances bioavailability of other compounds and inhibits MMP-9, reducing tissue damage during infection. Aloe polysaccharides support mucosal barrier integrity, providing protection against respiratory viral invasion. Standardized preparations optimize absorption and ensure consistent therapeutic effects.

Bilberry Extract contains anthocyanins that inhibit viral neuraminidase, particularly for influenza, and reduce HMGB 1 -mediated inflammation. It activates Nrf2 antioxidant pathways that protect tissues from oxidative damage during infection, consistent with polyphenolic antiinflammatory mechanisms. Bilberry compounds support vascular integrity, which is often compromised during severe viral infections. The overlap with anthocyanin effects from Vaccinium myrtillus reflects the importance of this botanical for vascular protection during infections.

Cat's Claw inhibits 3CLpro and NF-KB inflammatory pathways while reducing TNF-a production, with strong evidence for its immunomodulatory properties. Its alkaloid components provide immunomodulatory effects that balance antiviral responses, preventing excessive inflammation. Water extracts maximize pentacyclic oxindole alkaloid content, which is responsible for much of its immunomodulatory activity, while minimizing tetracyclic oxindole alkaloids that may have opposing effects. Cat's Claw supports tissue repair mechanisms that are essential for recovery from viral damage.

Piperine enhances bioavailability of other antiviral compounds by inhibiting intestinal glucuronidation and hepatic first-pass metabolism through CYP450 and UDP-glucuronyl transferase inhibition. It increases the bioavailability of co-administered compounds by up to 2-20 fold depending on the specific substance, making it a valuable adjunct in formulations. Preliminary data suggest it may modulate TMPRSS2 expression, although clinical evidence remains limited. Piperine is particularly effective when combined with poorly bioavailable flavonoids and polyphenols, creating synergistic therapeutic effects.

Aronia Extract inhibits viral attachment to host cells and suppresses IL-6 and STAT3 phosphorylation, effects documented for its anthocyanin constituents. Its anthocyanins provide powerful antioxidant protection against viral-induced oxidative stress and support vascular health, which is often compromised during severe viral infections. Fresh or minimally processed preparations preserve bioactive compounds, while enzymatic pre-treatment can enhance bioavailability of the polyphenolic constituents. The vascular protective effects are well- documented in the context of metabolic and inflammatory disorders.

Ursolic Acid directly inhibits viral proteases including 3CLpro and PLpro in computational studies while modulating the PI3K/Akt inflammatory pathway. It provides senomorphic benefits that support cellular resilience during and after viral infection. Its lipophilicity limits aqueous solubility and oral bioavailability, though nanoformulations and phospholipid complexes can significantly enhance its absorption. This triterpenoid demonstrates a triple mechanism targeting viral replication, inflammation, and tissue recovery.

Pelargonium Extract inhibits viral adhesion to host cells and increases ciliary beat frequency in respiratory tissues, effects that have been clinically documented for respiratory infections. It modulates TLR3 -mediated antiviral responses to enhance viral clearance, based on immunological studies. Pelargonium's diverse coumarins, phenolic acids, and flavonoids provide comprehensive protection against respiratory viral infections. Standardized liquid extracts maximize absorption of the active constituents, with prodrug coumarins being metabolized to active forms after absorption.

Black Rice Extract contains anthocyanins that inhibit NF-KB inflammatory pathways and NLRP3 inflammasome activation, effects well-established for rice-derived polyphenols. It activates SIRT1, providing anti-senescence benefits that support tissue recovery after viral infection. Black rice compounds demonstrate potent antioxidant activity that helps limit oxidative tissue damage during infection. Consumption with a small amount of healthy fat enhances absorption of the lipophilic components, while fermentation can increase bioavailability of bound phenolics.

Boswellia Extract inhibits 5-lipoxygenase and TNF-a inflammatory mediators while suppressing NF-KB signaling, mechanisms well-documented for boswellic acids. Its pentacyclic triterpene acids, particularly AKBA (3-O-acetyl-l l-keto-P-boswellic acid), reduce inflammatory tissue damage during viral infections. Boswellia compounds support respiratory function and tissue repair mechanisms essential for recovery from viral infections. AKBA has limited oral bioavailability (approximately 1%), which is enhanced when taken with fatty meals or through phospholipid formulations that improve absorption.

Use of the composition:

The compositions provided in the present invention are for use in treating a wide range of medical conditions, particularly but not exclusively those associated with viral infections and their complications, including multi-viral infections. These compositions are specifically designed to address complex pathophysiologies through a multi-targeted approach, combining active ingredients that work synergistically to combat various aspects of the disease process. For instance, in the context of respiratory diseases such as COVID-19, SARS, and MERS, the composition can simultaneously target viral replication, modulate the immune response, reduce inflammation, and support cellular repair mechanisms. This comprehensive approach aims to not only combat the viral infection itself but also to mitigate associated complications and support overall patient recovery. The versatility of these compositions extends to other viral infections such as influenza, RSV, and various human coronaviruses, offering a broad-spectrum therapeutic potential against respiratory pathogens.

According to an aspect of embodiments of the present invention, a method of treating a medical condition is provided, comprising administering to a patient in need thereof a therapeutically effective amount of any one of the compositions described in the present invention. This method is particularly effective for addressing inflammatory conditions such as lung inflammation, cytokine storm, and excessive immune responses often associated with severe viral infections. By leveraging the multi-warhead approach inherent in these compositions, the method aims to modulate various inflammatory pathways simultaneously, potentially reducing the severity and duration of inflammatory complications. Furthermore, this treatment method shows promise in addressing immune-related disorders, including viral-induced immune dysfunction, excessive NLRP3 inflammasome activation, and inflammatory stress. The comprehensive nature of the compositions allows for a nuanced approach to immune modulation, potentially restoring balance to dysregulated immune responses without compromising overall immune function.

The mode of administration for the compositions provided in this invention is primarily through oral routes, offering convenience and ease of use for patients. The recommended unit dose ranges from one to two grams (1-2 grams) of the composition per day for an adult human, which can be adjusted based on individual patient factors and the severity of the condition being treated. This dosage range is designed to provide therapeutic efficacy while minimizing the risk of adverse effects. The compositions can be formulated into various oral dosage forms, including but not limited to tablets, capsules, powders, suspensions, and solutions, allowing for flexibility in administration to suit patient preferences and clinical requirements. The oral route of administration facilitates consistent dosing and potentially enhances patient compliance, which is crucial for the effective management of both acute and chronic conditions.

The therapeutic applications of these compositions extend beyond respiratory and immune- related conditions. The method of treatment described herein also shows potential in addressing liver conditions such as liver dysfunction and viral-induced hepatic stress. The multi-targeted nature of the compositions allows for simultaneous support of liver function and protection against viral-induced damage, potentially improving overall liver health in patients affected by systemic viral infections. Additionally, the compositions show promise in addressing neurological conditions associated with viral infections, such as cognitive dysfunction and neural inflammation. By targeting multiple pathways involved in neuroinflammation and supporting cellular repair mechanisms, these compositions may offer neuroprotective benefits and potentially mitigate the long-term neurological sequelae associated with severe viral infections.

The compositions of the present invention are specifically designed for use in the treatment of a wide range of medical conditions, as described hereinabove, particularly those associated with viral infections and their complications.

Furthermore, the compositions of the invention are intended for use in the manufacturing of medicaments suitable for treating the aforementioned medical conditions. These medicaments can be formulated in various forms to optimize their efficacy, bioavailability, and ease of administration. The manufacturing process takes into account the synergistic effects of the multiple active ingredients, ensuring that the final medicament retains the multi-warhead approach central to the invention's therapeutic strategy. These medicaments can be produced in forms suitable for oral administration, including but not limited to tablets, capsules, powders, suspensions, and solutions, with dosages calibrated to deliver one to two grams of the composition per day for an adult human. The manufacturing process also considers factors such as stability, shelf-life, and potential interactions between components to ensure the medicament's quality and efficacy. By providing a basis for the production of such medicaments, the invention facilitates the translation of its novel therapeutic approach into practical, clinically applicable treatments for a range of challenging medical conditions associated with viral infections and their sequelae.

In summary, the compositions provided in this invention offer a versatile and comprehensive approach to treating a wide range of medical conditions, particularly those associated with viral infections and their complications. The multi- warhead strategy employed in these compositions, combined with the convenience of oral administration, presents a novel and potentially more effective approach to managing complex disease states. By simultaneously addressing multiple aspects of disease pathophysiology, these compositions aim to provide more comprehensive and efficient therapeutic outcomes compared to single-target approaches.

The compositions presented herein can therefore be used to combine active ingredients in a variety of nutraceutical or pharmaceutical compositions, and in the preparation of a variety of medicaments. Accordingly, there is provided a pharmaceutical composition or a medicament that includes any one of the compositions according to embodiments of the present invention, and a nutraceutical or pharmaceutically acceptable carrier. Similarly, there is provided a use of the compositions, according to embodiments of the present invention, in the preparation of a medicament. According to some embodiments of the present invention, the nutraceutical or pharmaceutical composition or the medicament comprising the same, are used to treat various medical conditions, as described in details hereinabove.

A “pharmaceutical composition” refers to a preparation which is in such form as to permit administration and subsequently provide the intended biological activity of the active ingredient(s) and/or to achieve a therapeutic effect, and which contains no additional components which are unacceptably toxic to a subject to which the formulation would be administered. The pharmaceutical composition may be sterile.

“Pharmaceutically acceptable” means approved or approvable by a regulatory agency of the Federal or a state government, or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia, for use in animals, and more particularly in humans. For example, the term “a pharmaceutically acceptable salt” may include, without limitation, hydrochloride (e.g., cetirizine dihydrochloride), sulfate (e.g., atorvastatin calcium sulfate), mesylate (e.g., imatinib mesylate), acetate (e.g., prednisolone acetate), citrate (e.g., tamoxifen citrate), tartrate (e.g., albuterol sulfate), maleate (e.g., enalapril maleate), phosphate (e.g., oseltamivir phosphate), lactate (e.g., ropinirole hydrochloride), and besylate (e.g., amlodipine besylate).

A “pharmaceutically acceptable carrier” or a “pharmaceutical excipient” comprises a material such as an adjuvant, a carrier, pH-adjusting and buffering agents, tonicity adjusting agents, wetting agents, preservative, and the like.

An “effective amount” of the composition(s), as disclosed herein, is an amount sufficient to perform treatment, or a specifically stated purpose, for example to produce a therapeutic effect after administration, such as, for example, a reduction in a symptom of a viral infection, or some other indicia of treatment efficacy. An effective amount can be determined in a routine manner in relation to the stated purpose. The term “therapeutically effective amount” refers to an amount of the herein-provided composition(s) effective to treat a medical condition (a disease or disorder) in a subject. A “prophylactically effective amount” refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. Typically, since a prophylactic dose is used in subjects prior to or at an earlier stage of disease, the prophylactically effective amount will be less than the therapeutically effective amount.

As used herein, “to treat” or “therapeutic” and grammatically related terms, refer to any improvement of any consequence of disease, such as prolonged survival, less morbidity, and/or a lessening of side effects which are the byproducts of an alternative therapeutic modality. As is readily appreciated in the art, full eradication of disease is encompassed but not required for a treatment act. Each of the terms “treatment”, “treating”, and “treat”, as used herein, refers to the administration of any one of the compositions provided herein or a nutraceutical/pharmaceutical composition/medicament comprising the same, to a subject, e.g., a patient. The treatment can be to cure, heal, alleviate, relieve, alter, remedy, ameliorate, palliate, improve or affect the disorder, the symptoms of the disorder or the predisposition toward the disorder, e.g., a respiratory viral infection. In some embodiments, in addition to treating a subject with a condition, a composition disclosed herein can also be provided prophylactically to prevent or reduce the likelihood of developing that condition.

The terms “subject” and “patient” are used interchangeably herein to refer to any animal, such as any mammal, including but not limited to, humans, non-human primates, rodents, and the like. In some embodiments, the mammal is a mouse. In some embodiments, the mammal is a human.

The present invention also relates to compositions that can be classified as medicinal or medical foods, food supplements, or additives for food and beverages. Medical foods are a distinct category of products intended for the specific dietary management of a disease or condition that has distinctive nutritional requirements. Unlike conventional foods or dietary supplements, medical foods are formulated to be consumed or administered enterally under the supervision of a physician and are designed to meet specific nutritional requirements for the management of a disease or condition. Food supplements, on the other hand, are concentrated sources of nutrients or other substances with a nutritional or physiological effect, marketed in dose form to supplement the normal diet. The compositions disclosed herein are contemplated to fall within these categories, particularly as medical foods or as additives to food and beverages. These compositions are designed to provide specific nutritional support for individuals with particular health conditions or nutritional needs. By incorporating these compositions into foods or beverages, or by consuming them as standalone supplements, individuals can potentially benefit from their targeted nutritional properties. The versatility of these compositions allows for their integration into various dietary regimens, making them accessible and convenient for consumers seeking to address specific health concerns through their diet. As such, the present invention offers a novel approach to nutritional supplementation that bridges the gap between conventional foods and targeted nutritional therapy.

General definitions:

As used herein the term “about” or “approximately,” refers to ±10 %. For example, the term “about 100 units” encompasses the value 100 units, as well as the values 90 units, 91 units, 92 units, 93 units, 94 units, 95 units, 96 units, 97 units, 98 units, 98 units, 99 units, 100 units, 101 units, 102 units, 103 units, 104 units, 105 units, 106 units, 107 units, 108 units, 109 units, and 110 units.

The terms "comprises", "comprising", "includes", "including", “having” and their conjugates mean "including but not limited to"; namely, as used herein, these terms are intended to be open-ended and not limiting. They indicate that the presence of the listed elements does not preclude the inclusion of additional, unrecited elements or method steps.

The term “consisting of’ means “including and limited to”.

The term "consisting essentially of" means that the composition, method or structure may include additional ingredients, steps and/or parts, but only if the additional ingredients, steps and/or parts do not materially alter the basic and novel characteristics of the claimed composition, method or structure.

The phrase “one or more” as used herein includes one, two, three, or more of the described elements or components and does not exclude any combinations or sub-combinations thereof.

The terms “preferred” or “preferably” indicate an example or embodiment that is more suitable or favorable under certain circumstances, but these terms are not intended to limit the scope of the invention or to suggest that other variations are excluded.

As used herein, the phrase “selected from the group consisting of’ includes all members of the recited group, each member of the recited group, and all possible combinations. For example, selected from the group consisting of A, B, and C, includes A, only, as well as B, only, as well as C, only, as well as A and B, as well as A and C, as well as B and C, and as well as A, B, and C.

The term “substantially,” when used in reference to a characteristic or parameter, means that the characteristic or parameter need not be absolute but is close enough to the specified value or condition so as to achieve the intended purpose or effect.

As used herein, the phrases "substantially devoid of" and/or "essentially devoid of" in the context of a certain substance, refer to a composition that is totally devoid of this substance or includes less than about 5, 1, 0.5 or 0.1 percent of the substance by total weight or volume of the composition. Alternatively, the phrases "substantially devoid of" and/or "essentially devoid of" in the context of a process, a method, a property or a characteristic, refer to a process, a composition, a structure or an article that is totally devoid of a certain process/method step, or a certain property or a certain characteristic, or a process/method wherein the certain process/method step is effected at less than about 5, 1, 0.5 or 0.1 percent compared to a given standard process/method, or property or a characteristic characterized by less than about 5, 1, 0.5 or 0.1 percent of the property or characteristic, compared to a given standard. Further alternatively, the terms "substantially" and/or "essentially " in the context of a characterizing property, means that the characterizing property is expressed to at least 99 %, at least 95 %, at least 90 % of its full or complete expression. For example, the phrase “the elements are maintained substantially in a certain configuration” should be read as “at least 99 % of the elements are maintained in the certain configuration.”

As used herein, the phrases "substantially devoid of" and/or "essentially devoid of" in the context of a certain substance, refer to a composition that is totally devoid of this substance or includes less than about 5, 1, 0.5 or 0.1 percent of the substance by total weight or volume of the composition. Alternatively, the phrases "substantially devoid of" and/or "essentially devoid of" in the context of a process, a method, a property or a characteristic, refer to a process, a composition, a structure or an article that is totally devoid of a certain process/method step, or a certain property or a certain characteristic, or a process/method wherein the certain process/method step is effected at less than about 5, 1, 0.5 or 0.1 percent compared to a given standard process/method, or property or a characteristic characterized by less than about 5, 1, 0.5 or 0.1 percent of the property or characteristic, compared to a given standard.

When applied to an original property, or a desired property, or an afforded property of an object or a composition, the term “substantially maintaining”, as used herein, means that the property has not change by more than 20 %, 10 % or more than 5 % in the processed object or composition.

The term “exemplary” is used herein to mean “serving as an example, instance or illustration”. Any embodiment described as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments and/or to exclude the incorporation of features from other embodiments.

The words “optionally” or “alternatively” are used herein to mean “is provided in some embodiments and not provided in other embodiments”. Any particular embodiment of the invention may include a plurality of “optional” features unless such features conflict.

As used herein, the singular form "a", "an" and "the" include plural references unless the context clearly dictates otherwise. For example, the term "a compound" or "at least one compound" may include a plurality of compounds, including mixtures thereof.

Throughout this application, various embodiments of this invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. The phrases “ranging/ranges between” a first indicate number and a second indicate number and “ranging/ranges from” a first indicate number “to” a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals therebetween.

As used herein the terms “process” and "method" refer to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, material, mechanical, computational and digital arts.

Terms used in the singular form shall also include the plural, and vice versa, unless context clearly indicates otherwise. Furthermore, words of any gender include all genders and are intended to cover all corresponding terms.

Unless otherwise defined, all technical and/or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and/or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.

Various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below find experimental support in the following examples.

EXAMPLES Reference is now made to the following examples, which together with the above descriptions, illustrate some embodiments of the invention in a non-limiting fashion.

EXAMPLE 1

EXAMPLE 2

EXAMPLE 3 EXAMPLE 4

Black rice extract 25% anthocyanines 150 mg 42.85 %wt

Litho spermum erythrorhizon root extract 100 mg 28.57 %wt

Sunflower lecithin 100 mg 28.57 %wt

EXAMPLE 5

Baicalin 90% pure (Scutellaria baicalensis root) 80 mg 17.8 %wt

Baicalein 98% pure (Scutellaria baicalensis root) 20 mg 4.4 %wt

Anthocyanins (Oryza sativa) 200 mg 43.4 %wt

Arnebia eu chroma 95% pure 1 mg 1.2 %wt

Phosphatidyl serine 20% pure 150 mg 33.3 %wt

Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.

All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting. In addition, any priority document(s) of this application is/are hereby incorporated herein by reference in its/their entirety.

Claims

WHAT IS CLAIMED IS:

1. A composition comprising: extract of plant A of a genus selected from the group consisting of Lithospermum, Arnebia, Coleus, Plectranthus, and Solenostemom, and extract of plant B of a genus selected from the group consisting of Oryza, Aronia, Vaccinium, Rubus, Prunus, Vitis, Solanum, Malus, Brassica, Dioscorea, Sambucus, Ribes, Fragaria, Citrus, and Ipomoea.

2. The composition of claim 1, wherein said plant A is of a Lithospermum genus.

3. The composition of claim 2, wherein said plant A is gromwell (Lithospermum erythrorhizon) .

4. The composition of any one of claims 1-3, where an amount of said extract of plant A ranges 30-60 %wt of the total weight of the composition.

5. The composition of any one of claims 1-4, wherein said plant B is of a Oryza genus.

6. The composition of claim 5, wherein said plant B is black rice Oryza sativa L).

7. The composition of any one of claims 1-6, where an amount of said extract of plant B ranges 30-60 %wt of the total weight of the composition.

8. The composition of any one of claims 1-7, further comprising at least one of: extract of plant C of a genus Scutellaria', and extract of plant D of a genus Boswellia.

9. The composition of claim 8, wherein said plant C is Scutellaria baicalensis.

10. The composition of any one of claims 8-9, where an amount of said extract of plant C ranges 10-40 %wt of the total weight of the composition.

11. The composition of any one of claims 8-10, wherein said plant D is selected from the group consisting of Boswellia sacra, Boswellia serrata, Boswellia papyrifera and Boswellia carteri.

12. The composition of any one of claims 8-11, where an amount of said extract of plant D ranges 20-60 %wt of the total weight of the composition.

13. A composition comprising: a shikonin; and an anthocyanin.

14. The composition of claim 13, where an amount of said shikonin ranges 2-15 %wt of the total weight of the composition.

15. The composition of any one of claims 13-14, where an amount of said anthocyanin ranges 30-50 %wt of the total weight of the composition.

16. The composition of any one of claims 13-15, further comprising at least one flavonoid selected from the group consisting of baicalin, baicalein, and wogonin.

17. The composition of any one of claims 13-16, further comprising at least one boswellic acid selected from the group consisting of incensole, incensole acetate, a-boswellic acid, P-boswellic acid, acetyl-P-boswellic acid, 11-keto-P-boswellic acid (KB A), acetyl- 11-keto-P- boswellic acid (AKBA), 3-O-acetyl-a-boswellic acid, 3-O-acetyl-P-boswellic acid, 3-O-acetyl-l l- keto-P-boswellic acid, lupeolic acid, and 3-O-acetyl-lupeolic acid.

18. The composition of any one of claims 1-17, further comprising at least one of: ivermectin; metformin; curcumin/nano-curcumin; and aspirin.

19. The composition of claim 18, where an amount of said ivermectin ranges 0.1-10 %wt of the total weight of the composition.

20. The composition of claim 18, where an amount of said metformin ranges 25-50

%wt of the total weight of the composition.

21. The composition of claim 18, where an amount of said nano-curcumin ranges 5-10 %wt of the total weight of the composition.

22. The composition of any one of claims 1-21, further comprising a lipid.

23. The composition of claim 22, wherein said lipid is selected from the group consisting of a glycerophospholipid, a sphingolipids and/or a sterol.

24. The composition of claim 23, wherein said glycerophospholipid is selected from the group consisting of phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol, phosphatidic acid, sphingomyelin and cholesterol.

25. The composition of any one of claims 22-24, wherein a source of said lipid is lecithin.

26. The composition of any one of claims 23-25, wherein an amount of said lipid ranges 5-15 %wt of the total weight of the composition.

27. A composition comprising: a viral protease inhibitor; an endogenous host protease inhibitor; an anti-inflammatory agent; and an anti-senescence agent.

28. The composition of claim 27, wherein said viral protease is selected from the group consisting of a 3CL protease inhibitor such as baicalin, baicalein, quercetin, epigallocatechin gallate (EGCG), curcumin/nano-curcumin, glycyrrhizin, and shikonin; a flavonoid such as quercetin, baicalein, and myricetin; a polyphenol such as epigallocatechin gallate (EGCG), resveratrol, and curcumin/nano-curcumin; a stilbenoid such as pterostilbene, hopeaphenol, and trans-8-vinifcrin; a lignan such as arctigenin, sesamin, and podophyllo toxin; an alkaloid such as berberine, camptothecin, and sanguinarine; a terpenoid such as glycyrrhizin, andrographolide, and betulinic acid; a quinone such as shikonin, tanshinone IIA, and emodin; a coumarin such as esculetin, psoralen, and scopoletin; a chaicone such as xanthohumol, licochalcone A, and isoliquiritigenin; a tannin such as punicalagin, chebulagic acid, and ellagic acid; a saponin such as ginsenoside Rg3, saikosaponin D, and astragaloside IV; a carotenoid such as lutein, lycopene, and P-carotene; an anthocyanin such as cyanidin, delphinidin, and malvidin; a sulfur-containing compound such as allicin, sulforaphane, and S-allyl cysteine; a peptide-based inhibitor such as cyclotide, lunasin, and sunflower trypsin inhibitor.

29. The composition of claim 28, wherein said viral protease is 3CL protease, and said viral protease inhibitor is an anthocyanin and/or shikonin.

30. The composition of claim 27, wherein said endogenous host protease inhibitor is selected from the group consisting of a cysteine protease inhibitor such as shikonin, tanshinone IIA, and betulinic acid; a flavonoid such as quercetin, kaempferol, baicalin, and baicalein; a polyphenol such as epigallocatechin gallate (EGCG), curcumin/nano-curcumin, and resveratrol; a stilbenoid such as pterostilbene, hopeaphenol, and trans-s-viniferin; a lignan such as arctigenin, sesamin, and podophyllo toxin; an alkaloid such as berberine, chelerythrine, and sanguinarine; a terpenoid such as boswellic acid, glycyrrhizin, and andrographolide; a quinone such as shikonin, tanshinone IIA, and emodin; a coumarin such as esculetin, psoralen, and scopoletin; a chaicone such as xanthohumol, licochalcone A, and isoliquiritigenin; a tannin such as punicalagin, chebulagic acid, and ellagic acid; a saponin such as ginsenoside Rg3, saikosaponin D, and astragaloside IV; a carotenoid such as lutein, lycopene, and P-carotene; an anthocyanin such as cyanidin, delphinidin, and malvidin; a sulfur-containing compound such as allicin, sulforaphane, and S-allyl cysteine; a peptide-based inhibitor such as cyclotide, lunasin, and sunflower trypsin inhibitor; a serine protease inhibitor such as boswellic acid, glycyrrhizin, and epigallocatechin gallate (EGCG); a matrix metalloproteinase (MMP) inhibitor such as curcumin/nano-curcumin, resveratrol, and baicalein; an elastase inhibitor such as a boswellic acid, frankincense resin, quercetin, and kaempferol.

31. The composition of claim 30, wherein said endogenous host protease is transmembrane serine protease 5, and said endogenous host protease inhibitor is an anthocyanin, a boswellic acid and/or shikonin.

32. The composition of claim 27, wherein said anti-inflammatory agent is selected from the group consisting of a flavonoid such as quercetin, kaempferol, baicalin and baicalein; a polyphenol such as epigallocatechin gallate (EGCG), resveratrol, and curcumin; a stilbenoid such as pterostilbene, hopeaphenol, and trans-s-viniferin; a lignan such as arctigenin, sesamin, and podophyllo toxin; an alkaloid such as berberine, chelerythrine, and sanguinarine; a terpenoid such as frankincense terpenoids, boswellic acids, and andrographolide; a quinone such as shikonin, tanshinone IIA, and emodin; a coumarin such as esculetin, psoralen, and scopoletin; a chaicone such as xanthohumol, licochalcone A, and isoliquiritigenin; a tannin such as punicalagin, chebulagic acid, and ellagic acid; a saponin such as ginsenoside Rg3, saikosaponin D, and astragaloside IV; a carotenoid such as lutein, lycopene, and P-carotene; an anthocyanin such as cyanidin, delphinidin, and malvidin; a sulfur-containing compound such as allicin, sulforaphane, and S-allyl cysteine; a peptide-based anti-inflammatory agent such as cyclotide, lunasin, and sunflower trypsin inhibitor; a nuclear factor-kappa B (NF-KB) inhibitor such as frankincense, curcumin, and andrographolide; a cytokine modulator such as quercetin, resveratrol, and baicalein; an inflammasome inhibitor such as curcumin/nano-curcumin, epigallocatechin gallate (EGCG), and tanshinone IIA; a cyclooxygenase (COX) inhibitor such as nano-curcumin, boswellic acids, and licochalcone A; a lipoxygenase (LOX) inhibitor such as anthocyanins, luteolin, and myricetin.

33. The composition of claim 32, wherein said anti-inflammatory agent is an anthocyanin, a boswellic acid such as incensole/incensole acetate and/or curcumin/nano-curcumin.

34. The composition of claim 27, wherein said anti-senescence agent is selected from the group consisting of a telomerase activator such as cycloastragenol, astragaloside IV, and Telomerase Activator 2 (TAT2); a senolytic agent such as quercetin, fisetin, and piperlongumine; an mTOR inhibitor such as metformin, rapamycin (sirolimus), everolimus, and resveratrol; an NAD+ booster such as nicotinamide riboside, nicotinamide mononucleotide (NMN), and niacin (vitamin B3); a sirtuin activator such as resveratrol, pterostilbene, and fisetin; an antioxidant and free radical scavenger such as vitamin C, vitamin E, and coenzyme Q10; a DNA repair enhancer such as shikonin, nicotinamide, Oxoguanine Glycosylase 1 (OGGI) activators, and Poly (ADP- ribose) Polymerase inhibitors (PARP inhibitors); an autophagy inducer such as spermidine, curcumin/nano-curcumin, and urolithin A; a mitochondrial function enhancer such as pyrroloquinoline quinone (PQQ), Mitoquinone (MitoQ), and SS-31 (elamipretide); an epigenetic modulator such as valproic acid, sodium butyrate, and epigallocatechin gallate (EGCG); a stem cell activator such as SB203580 (p38 Mitogen-Activated Protein Kinase inhibitor), Y-27632 (Rho- associated protein kinase inhibitor), and fucoidan; an inflammasome inhibitor such as MCC950, OLT1177, and tranilast; a senescence-associated secretory phenotype (SASP) inhibitor such as glucocorticoids, Janus Kinase inhibitors (JAK inhibitors) (ruxolitinib, tofacitinib), and apigenin; a proteostasis regulator such as 17- Allylamino- 17-demethoxygeldanamycin (17-AAG, tanespimycin), 17-Demethoxy-17-allylamino-geldanamycin (17-DMAG, alvespimycin), and arimoclomol; a cellular reprogramming factor such as octamer-binding transcription factor 4 (Oct4), sex-determining region Y-box 2 (Sox2), and Kruppel-like factor 4 (Klf4); a hormone replacement/modulator such as growth hormone, dehydroepiandrosterone (DHEA), and melatonin; an extracellular matrix (ECM) modulator such as hyaluronic acid, collagen peptides, and glucosamine; a caloric restriction mimetic such as 2-deoxyglucose, hydroxycitrate, and spermidine; an exercise mimetic such as 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR), GW501516, and SR9009; a genomic stability enhancer such as nuclear receptor binding to intronic DNA (NR-BID), LB- 100 (Protein Phosphatase 2A inhibitor, PP2A inhibitor), and an anthocyanin.

35. The composition of claim 34, wherein said anti-senescence agent is shikonin, metformin and/or an anthocyanin.

36. The composition of any preceding claim, for use in the treatment of a medical condition in a subject in need thereof.

37. Use of the composition of any preceding claim, for the manufacturing in the treatment of a medical condition in a subject in need thereof.

38. A method of treating a medical condition, comprising administering to a subject in need thereof a therapeutically effective amount of any one of the compositions of the preceding claims.

39. The composition of claim 36, or the use of claim 37, or the method of claim 38, wherein said medical condition is selected from the group consisting of a respiratory disease such as COVID-19, SARS, and MERS; a viral infection such as influenza, RSV, and human coronaviruses (hCoV-HKUl, hCoV-NL63, hCoV-229E); an inflammatory condition such as lung inflammation, cytokine storm, and excessive immune response; an immune-related disorder such as viral-induced immune dysfunction, excessive NLRP3 inflammasome activation, and inflammatory stress; a liver condition such as liver dysfunction and viral-induced hepatic stress; a neurological condition such as cognitive dysfunction and neural inflammation.

40. A medical food, comprising or consisting of the composition of any preceding claim.