[go: up one dir, main page]

WO2022115654A1 - Méthodes de traitement d'une infection au sars-cov-2 - Google Patents

Méthodes de traitement d'une infection au sars-cov-2 Download PDF

Info

Publication number
WO2022115654A1
WO2022115654A1 PCT/US2021/060889 US2021060889W WO2022115654A1 WO 2022115654 A1 WO2022115654 A1 WO 2022115654A1 US 2021060889 W US2021060889 W US 2021060889W WO 2022115654 A1 WO2022115654 A1 WO 2022115654A1
Authority
WO
WIPO (PCT)
Prior art keywords
agent
subject
plant
combination
cov
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2021/060889
Other languages
English (en)
Inventor
Shang-Cheng Hung
Chi-Huey Wong
Jia-Tsrong Jan
Ting-Jen Cheng
Che Ma
Rong-Jie Chein
Wen-Bin Yang
Ying-Ta Wu
Pi-Hui Liang
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Academia Sinica
Original Assignee
Academia Sinica
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Academia Sinica filed Critical Academia Sinica
Publication of WO2022115654A1 publication Critical patent/WO2022115654A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • A61K36/074—Ganoderma
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/282—Artemisia, e.g. wormwood or sagebrush
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/288—Taraxacum (dandelion)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/35—Caprifoliaceae (Honeysuckle family)
    • A61K36/355—Lonicera (honeysuckle)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/484—Glycyrrhiza (licorice)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/534—Mentha (mint)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/77—Sapindaceae (Soapberry family), e.g. lychee or soapberry
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/78—Saururaceae (Lizard's-tail family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/82—Theaceae (Tea family), e.g. camellia

Definitions

  • SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA coronavirus of the betacoronaviridae family and the pathogen is responsible for the global pandemic that causes the coronavirus induced disease in 2019 (COVID-19). Compared to the SARS-CoV and MERS-CoV outbreaks in 2002 and 2012, respectively, SARS-CoV-2 shows a lower fatality rate, but a much higher transmission rate, causing a greater threat to the public health and extraordinary social and economic burdens.
  • SARS-CoV-2 Infection of SARS-CoV-2 starts with the interaction of the trimeric viral spike (S) protein with human angiotensin-converting enzyme 2 (ACE2) receptor on airway epithelial cells, followed by viral entry and priming of human transmembrane protease serine 2 (TMPRSS2) that cleaves the S protein and initiates viral fusion.
  • TMPRSS2 human transmembrane protease serine 2
  • the viral genomic RNA is translated to polyprotein la (PPla) and polyprotein lab (PPlab), which are subsequently cleaved by a papain-like (PL) protease and a 3C-like (3CL) protease to form 16 non-structural proteins (Nspl-16) as a replication-transcription complex (RTC).
  • PPla polyprotein la
  • PPlab polyprotein lab
  • RNA-dependent RNA polymerase RNA-dependent RNA polymerase
  • the viral proteins further undergo post-translational modifications (such as glycosylation) at the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), after which they are transported to the cell membrane for exocytosis.
  • ERGIC endoplasmic reticulum-Golgi intermediate compartment
  • Remdesivir a Rdrp prodrug inhibitor
  • F avipiravir an inhibitor of influenza Rdrp
  • Hydroxychloroquine especially in combination with a zinc supplement, has been reported to exhibit antiviral activity against RNA viruses, but the clinical use of hydroxychloroquine alone for the treatment of COVID-19 was halted due to a lack of significant benefit.
  • RNA viruses have higher mutation rates than DNA viruses.
  • a protein interaction map revealed 332 human proteins interacting with 27 SARS-CoV-2 proteins; a phosphoproteomic approach was further employed to expand the study of viral-host interaction.
  • the proteomic analysis reported recently was only focused on the S protein and the detailed functions of glycosylation remained unclear.
  • the S protein is a promising target for development of neutralizing antibodies and vaccines due to its expression on the viral surface and its involvement in host cell entry.
  • the S protein is highly glycosylated and broadly mutated, with approximately 85% of the sequence being changed, indicating the challenge in the development of effective vaccines or antibodies with broadly protective activity and the need to develop alternative therapies.
  • development of new therapeutics often takes years; therefore, repurposing or repositioning of existing pharmaceuticals and herbal medicines for the treatment of COVID-19 has been considered as an attractive approach.
  • the present disclosure is based on the unexpected discoveries that some known compounds and herbal extracts are effective in suppressing the activity of SARS-CoV-2 both in vitro and in vivo, as such, these compounds and/or herbal extracts as described herein are potential candidates for the development of a medicament for treating SARS- CoV-2 infection.
  • the first aspect of the present disclosure to provide a method for treating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in a subject.
  • the method includes the step of administering to the subject an effective amount of an agent selected from the group consisting of an anti-viral agent, an anti- neoplastic agent, an anti-parasitic agent, an ion channel modulator, an antibiotic, an herbal extract, Soho tea, Reishi polysaccharide fraction 3 (RF3) of Ganoderma lucidum, and a combination thereof, so as to alleviate or reduce symptoms associated with the S ARS- CoV-2 infection.
  • an agent selected from the group consisting of an anti-viral agent, an anti- neoplastic agent, an anti-parasitic agent, an ion channel modulator, an antibiotic, an herbal extract, Soho tea, Reishi polysaccharide fraction 3 (RF3) of Ganoderma lucidum, and a combination thereof, so as to alleviate or reduce symptoms associated
  • anti-viral agent suitable for use in the present method include, but are not limited to, nelfinavir (N-Bn), nelfinavir mesylate, and boceprevir.
  • Example of the anti-neoplastic agent suitable for use in the present method includes, but is not limited to, cepharanthine.
  • Examples of the anti-parasitic agent suitable for use in the present method include, but are not limited to, emetine, ivermectin, moxidectin and mefloquine.
  • Examples of the ion channel modulator suitable for use in the present method include, but are not limited to, azelnidipine, dronedarone, ivacaftor and penfluridol [0016]
  • Examples of the antibiotic suitable for use in the present method include, but are not limited to, monensin, and maduramicin.
  • the agent is a combination of nelfinavir and ivermetin in a molar ratio of 1:1, a combination of cepharanthine and nelfinavir in a molar ratio of 2:1, or a combination of cepharanthine and ivermetin in a molar ratio of 2: 1.
  • the herbal extract suitable for use in the present method is a water extract of a plant selected from a group of families consisting of Lamiaceae, Mentheae, Asteraceae, Theaceae, Fabaceae,
  • Examples of the plant of Lamiaceae family includes but are not limited to, Metha arvensis, Mentha haplocalyx, Nepeta tenuifolia, Ocimum basilicum, Perilla folium, Perilla frutescens, Prunellae Spica, Prunella vulgaris, Salvia hispanica, and Salvia rosmarinus.
  • Example of the plant of Mentheae family includes, but is not limited to, Mentha haplocalyx or Metha arvensis.
  • Examples of the plant of Asteraceae family include, but are not limited to, Taraxacum mongolicum, Tussilago farfara, and Chrysanthemum morifolium.
  • Example of the plant of Theaceae family includes, but is not limited to, Camellia sinensis.
  • Examples of the plant of Fabaceae family include, but are not limited to, Arachis hypogaea, Glycyrrhiza uralensis, Glycyrrhiza glabra L, Glycyrrhiza inflate Batalin, and Spatholobus suberectus.
  • Examples of the plant of Saururaceae family includes, but are not limited to, Houttuynia cordata and Herba Houttuyniae.
  • Examples of the plant of Compositae family include, but are not limited to, Artemisia annua L., and Artemisia scoparia Waldst.
  • Examples of the plant of Sapindaceae family include, but are not limited to, Dimocarpus longan and Litchi chinensis.
  • Example of the plant of Caprifoliaceae family includes, but is not limited to,
  • the herbal extract includes at least one compound selected from the group consisting of a flavonoid, flavan-3-ol, a caffeic acid derivative, a monoterpene, a diterpene, and a triterpene.
  • the Soho tea is a water extract of a combination of Perilla folium, Mentha haplocalyx, Prunellae spica, Houttuynia cordata, Artemisia annua L.
  • Glycyrrhiza uralensis in which the Perilla folium, the Mentha haplocalyx, the Prunellae spica, the Houttuynia cordata, the Artemisia annua L., and the Glycyrrhiza uralensis are respectively present in the amount of 40-75%, 10-30%, 0.1-2%, 1-4%, 5-15% and 5-15% by weight or volume in the combination.
  • the Soho tea is a water extract of a combination of Perilla folium, Mentha haplocalyx, Prunellae spica, Houttuynia cordata, Lonicera japonica, Tussilago farfara, and Glycyrrhiza uralensis, in which the Perilla folium, Mentha haplocalyx, Prunellae spica, Houttuynia cordata, Lonicera japonica, Tussilago farfara, and Glycyrrhiza uralensis are respectively present in the amount of 40-75%, 10-30%, 0.1-2%, 1-4%, 1-10%, 1-10% and 5-15% by weight or volume in the combination.
  • the agent selected from the group consisting of an anti-viral agent, an anti-neoplastic agent, an anti-parasitic agent, an ion channel modulator, an antibiotic, and a combination thereof is administered in the amount of 0.01 to 500 mg/Kg to the subject.
  • the agent selected from the group consisting of selected from the group consisting of an herbal extract, Soho tea, Reishi polysaccharide fraction 3 (RF3) of Ganoderma lucidum, and a combination thereof is administered in the amount of 0.01 to 5 g/Kg to the subject.
  • the subject suitable for receiving treatment of the present disclosure include, but are not limited to, mammals.
  • the subject is a human.
  • FIG 1 Evaluations of cell protective effect of Chinese herbal medicines in serial dilutions. Anti-SARS-CoV-2 infection effects of selected Chinese herbal medicines as water extracts (1.0 g/20 mL H 2 O) and RF3 dissolved in H 2 O (0.25 mg/mL) were presented as Log2(dilution fold); and
  • FIG 2 In vivo anti-SARS-CoV-2 assay conducted in female golden Syrian hamsters.
  • FIG 3 Evaluation of anti-SARS-CoV-2 effect of Soho Tea (formulation #1) in mice.
  • A Body weight change after 6-day treatment.
  • B Virus elimination effect of Soho Tea
  • administered For convenience, certain terms employed in the specification, examples and appended claims are collected here. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of the ordinary skill in the art to which this invention belongs.
  • administered or “administration” are used interchangeably herein to refer a mode of delivery, including, without limitation, intraveneously, intramuscularly, intraperitoneally, intraarterially, intracranially, or subcutaneously administering an agent (e.g., a compound or a composition) of the present invention.
  • an agent e.g., a compound or a composition
  • the compound of the present disclosure or a salt, a solvate thereof is formulated into tablets for oral administration.
  • an effective amount refers to an amount effective, at dosages, and for periods of time necessary, to achieve the desired result with respect to the treatment of a disease.
  • an agent i.e., the present compound or herbal extract which decrease, prevents, delays or suppresses or arrests any symptoms of the SARS-CoV-2 infection would be effective.
  • An effective amount of an agent is not required to cure a disease or condition but will provide a treatment for a disease or condition such that the onset of the disease or condition is delayed, hindered or prevented, or the disease or condition symptoms are ameliorated.
  • the effective amount may be divided into one, two or more doses in a suitable form to be administered at one, two or more times throughout a designated time period.
  • the present disclosure is related to therapeutic agents suitable for treating SARS- CoV-2 infection in a subject. Accordingly, the main objective of the present disclosure is to provide a method for treating a subject having SARS-CoV-2 infection.
  • the method includes the step of administering to the subject an effective amount of an agent selected from the group consisting of an anti-viral agent, an anti-neoplastic agent, an anti-parasitic agent, an ion channel modulator, an antibiotic, an herbal extract, Soho tea, Reishi polysaccharide fraction 3 (RF3) of Ganoderma lucidum and a combination thereof, so as to alleviate or ameliorate symptoms associated with the SARS-CoV-2 infection.
  • an agent selected from the group consisting of an anti-viral agent, an anti-neoplastic agent, an anti-parasitic agent, an ion channel modulator, an antibiotic, an herbal extract, Soho tea, Reishi polysaccharide fraction 3 (RF3) of Ganoderma lucidum and a combination thereof,
  • anti-viral agent suitable for use in the present method examples include, but are not limited to, nelfinavir (N-Bn), nelfinavir mesylate, and boceprevir.
  • Example of the anti-neoplastic agent suitable for use in the present method includes, but is not limited to, cepharanthine.
  • Examples of the anti-parasitic agent suitable for use in the present method include, but are not limited to, emetine, ivermectin, moxidectin and mefloquine.
  • Examples of the ion channel modulator suitable for use in the present method include, but are not limited to, azelnidipine, dronedarone, ivacaftor and penfluridol [0054]
  • Examples of the antibiotic suitable for use in the present method include, but are not limited to, monensin, and maduramicin.
  • the agent is a combination of nelfinavir and ivermetin in a molar ratio of 1:1, a combination of cepharanthine and nelfinavir in a molar ratio of 2:1, or a combination of cepharanthine and ivermetin in a molar ratio of 2: 1.
  • the herbal extract suitable for use in the present method is a water extract of a plant selected from a group of families consisting of Lamiaceae, Mentheae, Asteraceae, Theaceae, Fabaceae, Compositae, Saururaceae, Sapindaceae and Caprifoliaceae families.
  • Examples of the plant of Lamiaceae family includes but are not limited to, Metha arvensis, Mentha haplocalyx, Nepeta tenuifolia, Ocimum basilicum, Perilla folium. ⁇ Perilla frutescens, Prunellae Spica, Prunella vulgaris, Salvia hispanica, and Salvia rosmarinus.
  • Example of the plant of Mentheae family includes, but is not limited to, Mentha haplocalyx or Metha arvensis.
  • Examples of the plant of Asteraceae family include, but are not limited to,
  • Taraxacum mongolicum Tussilago farfara, and Chrysanthemum morifolium.
  • Example of the plant of Theaceae family includes, but is not limited to, Camellia sinensis.
  • Examples of the plant of Fabaceae family include, but are not limited to, Arachis hypogaea, Glycyrrhiza uralensis, Glycyrrhiza glabra L., Glycyrrhiza inflate Batalin, and Spatholobus suberectus.
  • Examples of the plant of Saururaceae family includes, but are not limited to, Houttuynia cordata and Herba Houttuyniae.
  • Examples of the plant of Compositae family include, but are not limited to, Artemisia annua L., and Artemisia scoparia Waldst.
  • Examples of the plant of Sapindaceae family include, but are not limited to, Dimocarpus longan and Litchi chinensis.
  • Example of the plant of Caprifoliaceae family includes, but is not limited to,
  • the herbal extract includes at least one compound selected from the group consisting of a flavonoid (e.g., myricetin), flavan-3-ol (e.g., catechin or epigallocatechin gallate), a caffeic acid derivative (e.g., caftaric acid, rosmarinic acid methyl ester, or chlorogenic acid), a monoterpene (e.g., 1,
  • a diterpene e.g., camosic acid or patchouli alcohol
  • a triterpene e.g., ursolic acid
  • the agent selected from the group consisting of the anti-viral agent, the anti-neoplastic agent, the anti- parasitic agent, the ion channel modulator, the antibiotic, and a combination thereof is administered to the subject in the amount of is administered to the subject in the amount of 0.01 to 500 mg/Kg to the subject, such as 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08,
  • the agent is administered to the subject in the amount of 10 to 300 mg/Kg, such as 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,
  • the agent is administered to the subject in the amount of 20 to 250 mg/Kg, such as 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,
  • the agent selected from the group consisting of the herbal extract, the Soho tea, the Rcishi polysaccharide fraction 3 (RF3) of Ganoderma lucidum is administered to the subject in the amount of 0.01 to 5 mg/Kg to the subject, such as 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.10, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0,
  • the agent is administered to the subject in the amount of 0.05 to 3.5 mg/Kg, such as 0.05, 0.06, 0.07, 0.08, 0.09, 0.10, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0,
  • the agent is administered to the subject in the amount of 1.0 to 3.0 mg/Kg, such as 1.0,
  • a drink or "Soho tea" prepared by extracting a combination of herbs and rhizome with hot water in a ratio of 1: 1 to 1:1,000 by weight or by volume is administered to a subject to protect the subject from being infected by the SARS-CoV-2 virus, or to reduce the viral load therein after the subject is exposed to SARS-CoV-2 virus.
  • Prunella Spike Houttuynia cordata (or Heartleaf Houttuynia), Artemisia annua L (or
  • Capillary Wormwood Herb Capillary Wormwood Herb
  • Glycyrrhiza uralensis or liquorice root and rhizome
  • 1 to 1,000 parts (weight or volume) of hot water for sufficient time, such as 20 min, then remove the combination of herbs and rhizome (e.g., by filtering) to produce the drink, which is in the form of a solution.
  • the Perilla folium, the Mentha haplocalyx, the Prunellae spica, the Houtuynia cordata, the Artemisia annua L., and the Glycyrrhiza uralensis are respectively present in the amount of 40-75%, 10-30%, 0.1-2%, 1-4%, 5-15% and 5-15% by weight or volume in the combination.
  • Perilla Folium or Perilla
  • Mentha haplocalyx or Wild Mint Herb
  • Prunellae Spica or Prunella Spike
  • Houttuynia cordata or Heartleaf Houttu
  • the Perilla folium, Mentha haplocalyx, Prunellae spica, Houtuynia cordata, Lonicera japonica, Tussilago farfara, and Glycyrrhiza uralensis are respectively present in the amount of 40-75%, 10-30%, 0.1-2%, 1-4%, 1-10%, 1-10%, and 5-15% by weight or volume in the combination.
  • the Soho tea is given to the subject as a drink, which can be consumed without limitation for at least 12 days, thereby rendering a protective effect (i.e., anti-SARS-CoV-2) to the subject, in which the viral load in the subject after being exposed to SARS-CoV-2 virus is lower than that of a control subject (i.e., the subject that receive water instead of Soho tea for 12 days).
  • a protective effect i.e., anti-SARS-CoV-2
  • a control subject i.e., the subject that receive water instead of Soho tea for 12 days.
  • a further aspect of the present disclosure is to provide formulations for use in the present method.
  • one or more of the afore-described agents is/are formulated into dosage forms for administering to the subject.
  • the present formulation comprises one or more of the agents described above; and a pharmaceutically acceptable excipient.
  • the agent e.g., mefloquine, nelfinavir, Nel/Iver (1:1), Cepha/Iver (2:1), Cepha/Nel (2:1), or extracts of Ganoderma luciudum, Perilla frutescens and Mentha haplocalyx
  • the agent e.g., mefloquine, nelfinavir, Nel/Iver (1:1), Cepha/Iver (2:1), Cepha/Nel (2:1), or extracts of Ganoderma luciudum, Perilla frutescens and Mentha haplocalyx
  • the agent e.g., mefloquine, nelfinavir, Nel/Iver (1:1), Cepha/Iver (2:1), Cepha/Nel (2:1), or extracts of Ganoderma luciudum, Perilla
  • the agent e.g., mefloquine, nelfinavir, Nel/Iver (1:1), Cepha/Iver (2:1), Cepha/Nel (2:1) or extracts of Ganoderma luciudum, Perilla frutescens and Mentha haplocalyx
  • the agent e.g., mefloquine, nelfinavir, Nel/Iver (1:1), Cepha/Iver (2:1), Cepha/Nel (2:1) or extracts of Ganoderma luciudum, Perilla frutescens and Mentha haplocalyx
  • the agent e.g., mefloquine, nelfinavir, Nel/Iver (1:1), Cepha/Iver (2:1), Cepha/Nel (2:1) or extracts of Ganoderma luciudum, Perilla frutescens and Mentha haplocalyx
  • the agent e.g., mefloquine, nelfmavir, Nel/Iver (1:1), Cepha/Iver (2:1), Cepha/Nel (2:1), extracts of Ganoderma luciudum, Perilla frutescens, and Mentha haplocalyx, or extracts of Ganoderma luciudum, Perilla frutescens, and Metha arvensis
  • the agent may be present at a level of about 0.1% to 99% by weight, based on the total weight of the formulation. In some embodiments, the agent is present at a level of at least 1% by weight, based on the total weight of the formulation.
  • the agent is present at a level of at least 5% by weight, based on the total weight of the formulation. In still other embodiments, the agent is present at a level of at least 10% by weight, based on the total weight of the formulation. In still yet other embodiments, the agent is present at a level of at least 25% by weight, based on the total weight of the formulation.
  • the formulation is prepared in accordance with acceptable pharmaceutical procedures, such as described in Remington’s Pharmaceutical Sciences, 17 th edition, ed. Alfonoso R. Gennaro, Mack Publishing Company, Easton, Pa ( 1985) .
  • Pharmaceutically acceptable excipients are those that are compatible with other ingredients in the formulation and biologically acceptable.
  • the formulation is manufactured in accordance with the intended routes for its administration.
  • an enteric coating may be applied on the formulation so as to prevent the agent of the present invention from being degraded in the acidic environment or until it reaches the intestines of the subject.
  • the formulation may further include additional components that help deliver the agent of the present invention to its intended target site.
  • the agents constituted the sensitizer is enclosed in a liposome to prevent it from enzymatic degradation, and to help transporting the agents through the circulation system of the subject, and/or across cell membrane to its intended cellular target site.
  • the least soluble agent of the sensitizer may be formulated with additional agents, such as a solvating agent, an emulsifying agent and/or a surfactant, into a liquid formulation.
  • additional agents include, but are not limited to, cyclodextrin (e.g., a-cyclodextrin and b-cyclodextrin), and non-aqueous solvents, which include but are not limited to, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propyl glycol, 1,3 -butyl glycol, dimethyl formamide, dimethyl sulfoxide, biocompatible oils (e.g., cottonseed oil, peanut oil, com oil, wheat germ oil, castor oil, olive oil, sesame oil, glycerol, tetrahydrogen furan, polyethylene glycol (PEG), fatty acid esters of cyclodextrin
  • formulations for acute treatment will contain larger amounts of the sensitizer, as compared to formulations that are for chronic treatment.
  • parental formulations will comprise less amounts of the present sensitizer, as compared to formulations that are for oral ingestion.
  • formulations suitable for other administration routes are also within the scope of the present disclosure.
  • Formulations may be in the form of liquids, solutions, suspensions, emulsions, elixirs, syrups, tablets, lozenges, granules, powders, capsules, cachets, pills, ampoules, suppositories, pessaries, ointments, gels, pastes, creams, sprays, mists, foams, lotions, oils, boluses, electuaries, or aerosols.
  • the agent of the present disclosure may be formulation into compositions suitable for oral ingestion.
  • Formulations suitable for oral administration e.g. by ingestion
  • a tablet may be made by conventional means, e.g., compression or molding, optionally with one or more accessory ingredients.
  • Compressed tablets may be prepared by compressing in a suitable machine the active compound in a free-flowing form such as a powder or granules, optionally mixed with one or more binders (e.g. povidone, gelatin, acacia, sorbitol, tragacanth, hydroxypropylmethyl cellulose); fillers or diluents (e.g. lactose, microcrystalline cellulose, calcium hydrogen phosphate); lubricants (e.g. magnesium stearate, talc, silica); disintegrants (e.g. sodium starch glycolate, cross-linked povidone, cross-linked sodium carboxymethyl cellulose); surface-active or dispersing or wetting agents (e.g.
  • binders e.g. povidone, gelatin, acacia, sorbitol, tragacanth, hydroxypropylmethyl cellulose
  • fillers or diluents e.g. lactose, microcrystalline cellulose, calcium
  • Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent.
  • the tablets may optionally be coated or scored and may be formulated so as to provide slow or controlled release of the active compound therein using, for example, hydroxypropylmethyl cellulose in varying proportions to provide the desired release profile.
  • Tablets may optionally be provided with an enteric coating, to provide release in parts of the gut other than the stomach.
  • Formulations suitable for parenteral administration include aqueous and nonaqueous isotonic, pyrogen-free, sterile injection solutions which may contain antioxidants, buffers, preservatives, stabilizers, bacteriostats, and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non- aqueous sterile suspensions which may include suspending agents and thickening agents, and liposomes or other mieroparticulate systems which are designed to target the agent to blood components or one or more organs.
  • aqueous and nonaqueous isotonic, pyrogen-free, sterile injection solutions which may contain antioxidants, buffers, preservatives, stabilizers, bacteriostats, and solutes which render the formulation isotonic with the blood of the intended recipient
  • aqueous and non- aqueous sterile suspensions which may include suspending agents and thickening agents, and liposomes or other mieroparticulate systems which are designed to
  • Suitable isotonic vehicles for use in such formulations include Sodium Chloride Injection, Ringer's Solution, or Lactated Ringer's Injection.
  • the formulations may be presented in unit-dose or multi- dose sealed containers, for example, ampoules and vials, and may be stored in a freeze- dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example water for injections, immediately prior to use.
  • sterile liquid carrier for example water for injections, immediately prior to use.
  • Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules, and tablets.
  • Formulations may be in the form of liposomes or other nanoparticulate or microparticulate systems which are designed to target the active compound to blood components or one or more organs.
  • Transmembrane formulations are those suitable for topical and tansmucosal uses, which include but are not limited to, ophthalmic solutions, sprays, aerosols, creams, lotions, ointments, gels, solutions, suspensions, skin patches and the like.
  • the patches include reservoir type and matrix type skin patches, and may adhere onto the skin for a certain period of time to allow the active component to be adsorbed into the subject's body.
  • inert excipients for topical administration, a wide variety of dermatologically acceptable inert excipients well known to the art may be employed. Typical inert excipients may be, for example, water, ethyl alcohol, polyvinyl pyrrolidone, propylene glycol, mineral oil, stearyl alcohol and gel-producing substances. All of the above dosages forms and excipients are well known to the pharmaceutical art. The choice of the dosage form is not critical to the efficacy of the composition described herein.
  • the agent of the present disclosure may also be formulated in a variety of dosage forms for mucosal application, such as buccal and/or sublingual drug dosage units for drug delivery through oral mucosal membranes.
  • dosage forms for mucosal application such as buccal and/or sublingual drug dosage units for drug delivery through oral mucosal membranes.
  • a wide variety of biodegradable polymeric excipients may be used that are pharmaceutically acceptable, provide both a suitable degree of adhesion and the desired drug release profile, and are compatible with the active agents to be administered and any other components that may be present in the buccal and/or sublingual drug dosage units.
  • the polymeric excipient comprises hydrophilic polymers that adhere to the wet surface of the oral mucosa.
  • polymeric excipients include, but are not limited to, acrylic acid polymers and copolymers; hydrolyzed polyvinyl alcohol; polyethylene oxides; polyacrylates; vinyl polymers and copolymers; polyvinylpyrrolidone; dextran; guar gum; pectins; starches; and cellulosic polymers.
  • the agent of the present disclosure may also be formulated in a dosage form for inhalation through nose or mouth, a solution or suspension containing the agent of the present disclosure and a pharmaceutical excipient generally accepted for this purpose is inhaled through an inhalant aerosol spray.
  • the agent of the present disclosure in the form of a powder may be administered through inhalator that allows direct contact of the powder with the lung.
  • pharmaceutical acceptable carriers such as isotonic agents, preservatives, dispersions, or stabilizers may be added. Further, if necessary, these formulations may be sterilized by filtration, or by treatment with heat or irradiation.
  • African green monkey kidney Vero E6 cells were grown in Minimum essential medium (Eagle) in Earle's BSS supplemented with 10% FBS, 2 mM 1-glutamine, 1 mM pyruvate, 0.1 mM non-essential amino acids and 1.5 g/L sodium bicarbonate at 37°C in the presence of 5% CO 2 atmosphere.
  • Soho Tea was prepared by extracting a total of 11.0 grams of herbs in 350 mL hot water for 20 min in accordance with the formulations described in Table 1.
  • the cytotoxicity of compound to the Vero E6 cells was assayed using the CCK- 8 cell counting kit (Dojindo Labortories) according to the manufacturer’s protocol. Briefly, after incubation with the indicated compounds at various concentrations for 24 h, 10 ⁇ L of the CCK-8 reagent were added to each well of the 96-well plate and placed in a CO 2 incubator for 1 to 4 h to react. The absorbance was measured with a spectrophotometer (SpectraMax M2, Molecular Devices) at 450 nm. Data are expressed as percentage of control cells (as 100%) cultured in the absence of compounds.
  • Nsp5 was incubated with Fluorescein-AVLQSGFRK(QXL520)-NH 2 in the absence or presence of indicated inhibitors in 20 mM Tris-HCl (pH 7.0) at 30°C for 30 minutes. The reaction was monitored with fluorescence (ex480/em530) with a plate reader and the initial velocity was calculated. The curves were fitted using Prism (Graphpad).
  • Treatment groups were given through oral administration twice a day with any one of mefloquine, nelfinavir, salinomycin, or thioguanine at a dose of 30 mg/kg/day, leaves of Perilla frutescens (200 mg/kg/day), leaves of Mentha haplocalyx (200 mg/kg/day), and extract of Ganoderma lucidum (30 mg/kg/day), while the control group was given an equal volume of drinking water.
  • all the hamsters were euthanized and the lung tissues were harvested for live viral load measurement by TCID50 assay in Vero E6 cells.
  • compound(s) having the ability to suppress S ARS-CoV -2 were screened from the compound library (which included herbal extracts) constructed in accordance with the procedures described in the "Materials and Methods" section using cell-based assays.
  • the antiviral activity of a candidate compound was assessed by visualization of the extent of cytopathogenic effect (CPE) on Vero E6 cells when infected with a strain of SARS-CoV-2 at concentrations of 10 pM, 3.3 pM and 1 pM respectively (or in the range from 1 nM to 100 nM for potent compounds). Of the 2,855 compounds tested, 15 were found to exhibit protective effects on Vero E6 cells. The activities of these compounds were evaluated on day-3 and day-5, and the minimal concentrations that showed protective effect are summarized in Table 2, in which the concentration of drugs required to inhibit 50% (IC50) of virus replication along with their 50% cytotoxicity (CC50) are shown.
  • CPE cytopathogenic effect
  • nelfmavir, nelfmavir mesylate, and nelfmavir derivative (Bn) respectively inhibited 3CL main protease with an IC50 of 56 + 15.8 mM, 33.4 + 6.2 mM, and 35 + IImM.
  • the library used in the screening process also contained several other clinically approved HIV protease inhibitors, including indinavir sulfate, saquinavir mesylate, atazanavir, ritonavir, darunavir, amprenavir, and lopinavir, and the HCV protease inhibitors daclatasvir, danoprevir and telaprevir, however, none of these compounds possessed inhibitory effects against SARS-CoV-2 in the concentrations used in the screening (data not shown).
  • viral polymerase inhibitors including acyclovir, famciclovir, penciclovir, ribavirin, cidofovir and entecavir, and reverse transcriptase inhibitors, including zalcitabine, nevirapine, efavirenz, abacavir sulfate, tenofovir disoproxil fumarate, adefovir dipivoxyl, delavirdine and telbivudine were also screened in the cell-based assay but no active compound was identified (data not shown).
  • These herbs contain flavonoids e.g., (myricetin), flavan-3-ol (e.g., catechin and epigallocatechin gallate), caffeic acid derivatives (e.g., caftaric acid, rosmarinic acid methyl ester, and chlorogenic acid, however, whether they are related to the antiviral activity remains to be investigated. It was reported that monoterpenes (1, 8-cineole and camphor from basil leaves), diterpenes (camosic acid and patchouli alcohol), and triterpenes (e.g., ursolic acid) were able to block virus entry and replication.
  • flavonoids e.g., (myricetin), flavan-3-ol (e.g., catechin and epigallocatechin gallate), caffeic acid derivatives (e.g., caftaric acid, rosmarinic acid methyl este
  • Example 2 In vivo Anti-SARS-CoV-2 activity of the compounds or herbal extracts identified in Example 1.
  • the drugs and herbal extracts identified from the cell-based assay in Example 1 were subject to animal study in accordance with the procedures described in "Materials and Methods" section. Specifically, 4 drugs including mefloquine, nelfinavir, salinomycin, and thioguanine; and three active herbal extracts including RF3, Perilla frutescens, and Mentha haplocalyx, were subject to evaluatation of their viral eradicating efficacy in female golden Syrian hamsters. Results are illustrated in FIG 2. [0137] Salinomycin was shown to cause higher weight loss than the control group
  • Example 3 In vivo Anti-SARS-CoV-2 activity of Soho tea [0139]
  • Soho tea prepared in accordance with procedures described in "Materials and Methods" section was given to hamster that had been exposed to SARS- CoV-2 virus as drinking water, and changes in the body weight, lung virus titer were determined.
  • Results are depicted in FIG 3 and Table 4, [0140] After giving Soho tea to hamster as drinking water, the lung virus titer was reduced to a level lower than the detection limit in both virus elimination (FIG 3, (B)) and protection experiments (FIG 3, (C)) without apparent weight loss (FIG 3, (A)), [0141] Comparative studies on the efficacies of two Soho tea formulations (# 1 and #2) against SARS-CoV2 were conducted, in which the SARS-CoV2 infected mice were treated with formulations # 1 and #2 for 6 days, then lung virus titers were determined. Results are summarized in Table 4. It was found that formulation # 2 of the Soho tea conferred a better protective effect over that of the formulation # 1.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La divulgation concerne des méthodes pour le traitement de l'infection par le coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2). La méthode comprend l'étape consistant à administrer à un sujet souffrant d'une infection au SARS-CoV-2 une quantité efficace d'un agent choisi dans le groupe constitué par un agent antiviral, un agent antinéoplasique, un agent antiparasitaire, un modulateur de canal ionique, un antibiotique, un extrait de plante, du thé Soho, une fraction de polysaccharide de Reishi 3 (RF3) de Ganoderma lucidum et une combinaison de ceux-ci, de façon à soulager ou à réduire les symptômes associés à l'infection au SARS-CoV-2.
PCT/US2021/060889 2020-11-30 2021-11-26 Méthodes de traitement d'une infection au sars-cov-2 Ceased WO2022115654A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202063119573P 2020-11-30 2020-11-30
US63/119,573 2020-11-30

Publications (1)

Publication Number Publication Date
WO2022115654A1 true WO2022115654A1 (fr) 2022-06-02

Family

ID=81756148

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2021/060889 Ceased WO2022115654A1 (fr) 2020-11-30 2021-11-26 Méthodes de traitement d'une infection au sars-cov-2

Country Status (2)

Country Link
TW (1) TWI876111B (fr)
WO (1) WO2022115654A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113209087A (zh) * 2020-02-05 2021-08-06 歌礼药业（浙江）有限公司 一种抑制冠状病毒的药物组合物及其用途
KR102524088B1 (ko) * 2022-10-27 2023-04-21 한국 한의학 연구원 한약재 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방, 개선 또는 치료용 조성물
US20240390269A1 (en) * 2023-05-26 2024-11-28 Ying-Ling Huang Use of perilla in the manufacture of medicament for inhibition of covid-19 virus

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060153803A1 (en) * 2003-06-09 2006-07-13 Tan Emily L C Inhibition of sars coronavirus infection with clinically approved antiviral drugs
US20180042909A1 (en) * 2015-03-31 2018-02-15 Mymd Pharmaceuticals, Inc. Methods of Treating Cancers, Autoimmune Disorders, and Other Conditions Associated with Chronic Inflammation
US20190307722A1 (en) * 2016-10-21 2019-10-10 Universite Claude Bernard Lyon 1 Antiviral compositions for the treatment of infections linked to coronaviruses
WO2020214716A1 (fr) * 2019-04-17 2020-10-22 Gilead Sciences, Inc. Inhibiteurs de la protéase du vih à base de 2-imino-5-oxo-imidazolidine
US20200362044A1 (en) * 2020-04-27 2020-11-19 Incelldx, Inc. Methods of Treating Cytokine Storm Infections, Including COVID-19, By Inhibiting CCR5/CCL5 (RANTES) Interaction, and Compositions for Practicing the Same

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111803593A (zh) * 2020-02-13 2020-10-23 邓润华 一种抗病毒中药组合物、制备方法及其应用

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060153803A1 (en) * 2003-06-09 2006-07-13 Tan Emily L C Inhibition of sars coronavirus infection with clinically approved antiviral drugs
US20180042909A1 (en) * 2015-03-31 2018-02-15 Mymd Pharmaceuticals, Inc. Methods of Treating Cancers, Autoimmune Disorders, and Other Conditions Associated with Chronic Inflammation
US20200179367A1 (en) * 2015-03-31 2020-06-11 Mymd Pharmaceuticals, Inc. Method of Treating Coronavirus
US20190307722A1 (en) * 2016-10-21 2019-10-10 Universite Claude Bernard Lyon 1 Antiviral compositions for the treatment of infections linked to coronaviruses
WO2020214716A1 (fr) * 2019-04-17 2020-10-22 Gilead Sciences, Inc. Inhibiteurs de la protéase du vih à base de 2-imino-5-oxo-imidazolidine
US20200362044A1 (en) * 2020-04-27 2020-11-19 Incelldx, Inc. Methods of Treating Cytokine Storm Infections, Including COVID-19, By Inhibiting CCR5/CCL5 (RANTES) Interaction, and Compositions for Practicing the Same

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KA-TIM CHOY; WONG ALVINA YIN-LAM; KAEWPREEDEE PRATHANPORN; SIA SIN FUN; CHEN DONGDONG; HUI KENRIE PUI YAN; CHU DANIEL KA WING; CHA: "Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro", ANTIVIRAL RESEARCH, vol. 178, 4 March 2020 (2020-03-04), pages 1 - 5, XP055738838 *
OHASHI ET AL.: "Multidrug treatment with nelfinavir and cepharanthine against COVID-19", BIORXIV, 15 April 2020 (2020-04-15), pages 1 - 12, XP055825394, Retrieved from the Internet <URL:https://www.biorxiv.org/content/10.1101/2020.04.14.039925v1> [retrieved on 20220314] *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113209087A (zh) * 2020-02-05 2021-08-06 歌礼药业（浙江）有限公司 一种抑制冠状病毒的药物组合物及其用途
CN113209087B (zh) * 2020-02-05 2023-11-07 歌礼药业（浙江）有限公司 一种抑制冠状病毒的药物组合物及其用途
KR102524088B1 (ko) * 2022-10-27 2023-04-21 한국 한의학 연구원 한약재 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방, 개선 또는 치료용 조성물
US20240390269A1 (en) * 2023-05-26 2024-11-28 Ying-Ling Huang Use of perilla in the manufacture of medicament for inhibition of covid-19 virus

Also Published As

Publication number Publication date
TW202224679A (zh) 2022-07-01
TWI876111B (zh) 2025-03-11

Similar Documents

Publication Publication Date Title
Li et al. Antiviral activities of medicinal herbs traditionally used in southern mainland China
TWI876111B (zh) 治療嚴重急性呼吸道症候群乙型冠狀病毒感染的方法
CN111888434B (zh) 一种抗冠状病毒的中药颗粒剂及其制备方法和用途
KR102131043B1 (ko) 인삼열매 다당체를 포함하는 인플루엔자 바이러스 감염 예방 또는 억제용 조성물
CN102180853B (zh) 抗ev71的黄酮类化合物，及其在制药中的应用
WO2016169573A1 (fr) Lactones sesquiterpéniques en tant que composés antiviraux puissants et à large spectre contre tous les génotypes du virus de l&#39;hépatite c (vhc)
CN112076262A (zh) 一种中药组合物在制备预防和治疗新型冠状病毒感染肺炎药物中的应用
WO2021179950A1 (fr) Utilisation d&#39;une composition pharmaceutique dans la préparation d&#39;un médicament antiviral
CN112386595A (zh) 一种治疗呼吸系统病毒性感染的药物组合物
CN114732853B (zh) 一种中药组合物在抗冠状病毒、保护脏器、提高免疫力药物中的应用
EA017705B1 (ru) Способ подавления ортопоксвирусных инфекций
CN111728965A (zh) 化合物在制备抗病毒药物中的应用
CN119950474A (zh) 异绿原酸c在制备抗呼吸道合胞病毒a型株药物中的应用
CN113975268B (zh) 5,6-dehydroeurycomalactone在制备抗登革病毒药物的应用
CN102416167B (zh) 干扰素α与硫酸特布他林的雾化吸入剂
CN103623042B (zh) 一种景天清肺药物组合物在制备抗甲型流感病毒药物中的应用
US20080102140A1 (en) Use of solidago virgaurea in the treatment and prevention of viral infections
CN113855688A (zh) Vina-ginsenoside R18在制备抗登革病毒药物制剂中的应用
CN102416168B (zh) 干扰素α与氨溴索的雾化吸入剂
CN106243102B (zh) 生物碱类化合物的应用
CN113952457A (zh) 泰瑞米特或含有泰瑞米特的药物组合物在抗冠状病毒中的应用
CN106336447B (zh) 南蛇藤素的应用
KR102451254B1 (ko) 코로나바이러스 감염증의 예방, 경감 또는 치료용 약학 조성물
US20250195553A1 (en) Use of Genipin-1-B-D-Gentiobioside in Preparation of Drug
CN102416165B (zh) 干扰素α与地塞米松磷酸钠的雾化吸入剂

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21899152

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21899152

Country of ref document: EP

Kind code of ref document: A1