MX2008000363A - Composition and the use thereof for the treatment of viral infections - Google Patents

Abstract

The present invention relates to improved methods and compositions for treating viral infections and other diseases and conditions that induce a cytokine storm. The present invention also relates to novel compositions comprising quercitin or derivatives thereof, at least one calcium channel blocker component, an anticonvulsant component, a quinoline component or derivatives thereof, and a multivitamin component, in sufficient amounts to treat and reduce viral activity in the cell or subject.

Description

COMPOSITION AND USE OF THE SAME FOR THE TREATMENT OF VIRAL INFECTIONS FIELD OF THE INVENTION The present invention relates to improved methods and compositions for the treatment of viral infections and other diseases and conditions that induce a cytosine crisis. The present invention also relates to novel compositions comprising quercetin or derivatives thereof, at least one component of the calcium channel blocker, an anti-convulsant component, a quinoline component or derivatives thereof and a multi-vitamin component, in sufficient amounts to treat and reduce viral activity in the cell or subject. BACKGROUND OF THE INVENTION The present invention relates to improved methods and compositions for the treatment of viral infections including retroviruses and hepadnaviruses, such as HIV and Hepatitis C, in infected subjects. The disease now known as acquired immunodeficiency syndrome (AIDS) was first recognized as long ago as in 1979. The number of cases reported to the Centers for Disease Control and Prevention (CDC) has increased dramatically each year since then, and in 1982, the CDC declared AIDS a new epidemic. It has been estimated that more than 40 million - - people have been diagnosed with AIDS. Retroviruses were proposed as the causative agent of AIDS, with the human immunodeficiency virus type 1 (HIV-1) emerging as the preferred name for the virus responsible for the progression of AIDS. Antibodies to HIV are present in more than 80% of subjects diagnosed with AIDS or pre-AIDS syndrome and have also been found with high frequency, in groups identified as high risk AIDS groups. AIDS is characterized by a compromised immune system attributed to the systemic reduction of CD4 + T lymphocytes (T-cells), as well as the lack of response and incompetence of the remaining CD4 + T cells in the immune system. The level of CD4 + T cells serves as a diagnostic indicator of the progression of the disease. It is known that CD4 + T cells infected with HIV are directly cytopathic to other CD4 + T cells and this single cell eliminating event is initiated by interactions between the HIV envelope protein interaction (gp 120/41) and the CD4 receptor molecule in host cells. Highly virulent HIV isolates isolate syncytia (defined as> 4 nuclei within a common cell membrane), a process associated with the rapid loss of CD4 + T cells and the progression of the disease. HIV infection in humans results in general immunosuppression and may involve other disorders, such as blindness, myelopathy and dementia neurological disorders, such as, for example, the AIDS dementia complex, a common and important cause of morbidity in subjects in advanced stages of infection. HIV infection has been documented in several areas of the CNS, including the cerebral cortex, spinal cord, and retina. Price et al. , (1988, Science 239: 586) and Ho et al. , (1989, Annals in Infernal Medicine 111: 400) reviewed the clinical, epidemiological and pathological aspects of the AIDS dementia complex and suggest that the mechanism underlying neurological dysfunction may be indirect tissue damage. either by toxic substances of viral or cellular derivation released by the infected cells. There is considerable difficulty in diagnosing the risk of developing AIDS. It is known that AIDS eventually develops in almost all individuals infected with HIV. A subject is usually diagnosed with AIDS when a previously healthy adult with an intact immune system acquires impaired immunity from the T-cell. Deteriorated immunity usually appears over a period of 18 months to 3 years. As a result of this impaired immunity, the subject becomes susceptible to opportunistic infections, various types of cancer, such as Kaposi's sarcoma, non-Hodgkins lymphoma, and other disorders associated with reduced functioning of the immune system. HIV replicates through a DNA intermediary. Each virus particle contains two identical single-stranded RNA molecules surrounded by the nucleocapsid viral protein. The remaining part of the virus core is composed of the capsid and matrix proteins. The enzymes required for the integration replication of viral genetic materials in host cells are also contained within the capsid. The outer envelope of the virus particle comprises viral envelope glycoproteins and a membrane derived from the host cell. A sufficiently effective treatment is not available, capable of preventing the progression towards AIDS although HAART (highly active anti-retroviral therapy) has partially reversed the immunodeficiency caused by AIDS. Essentially, all subjects with opportunistic infections and approximately half of the subjects with Kaposi's sarcoma have died within two years of diagnosis. Attempts to revive the immune system in subjects with AIDS have been, until now, substantially unsuccessful. Although 3 'azido-3' deoxythymidine (AZT) has been used more frequently in the treatment of HIV infection and AIDS, it has considerably negative side effects, such as a reversible toxicity of the bone marrow and the development of viral resistance. to AZT by the subject. Therefore other methods of treatment are highly desirable. Influenza virus, like that of HIV, is a single-stranded RNA virus enveloped. The influenza viruses belong to the Orthomyxoviridae virus family. There are three serotypes of influenza viruses: A, B and C. Influenza A occurs more frequently and is also the most virulent form, being responsible for most epidemics and influenza pandemics. Influenza A can also be classified as a sub-type based on antigens H (haemagglutinin- the protein responsible for binding the influenza virus to host cells) surface and N (neuraminidase), which are the main antigenic determinants. Influenza strains can also be classified based on the geographic location of the first isolated strain, serial number and year of isolation. In recent years, outbreaks of the highly pathogenic H5N1 strains of avian influenza species (a type of influenza A) have caused significant concern. In 1997 an outbreak of H5N1 in Hong Kong spread rapidly through poultry and as a result millions of these were discarded. The H5N1 virus has continued to spread, resulting in outbreaks in poultry throughout Asia and also, more recently, in Russia, Romania and Turkey. Of particular concern is the fact that the H5N1 virus can cross the species barrier. There have already been numerous cases of direct transmission of the virus from poultry to humans, resulting in almost a 50% mortality rate among those infected humans. H5N1 infects epithelial cells and causes a rampant pro-inflammatory immune response that induces the so-called "cytokine crisis". The induction of this cytokine crisis is one of the main causes of pathogenicity since it leads to the death of epithelial cells, to a syndrome of acute respiratory distress and in many cases to death. There is concern that the H5N1 virus may evolve through a minor antigenic variation to generate a form capable of human-to-human transmission. Therefore, there is great concern about the possibility of a future human pandemic that could result in millions of deaths worldwide. The neuraminidase inhibitor Oseltamivir (Tamiflu ™) is currently the main treatment option for avian influenza, and the stockpiling of this drug is part of the plans of - pandemic preparation in the U.S. and in other parts. However, Tamiflu ™ resistant H5N1 variants were recently isolated in two patients who died from infection (de Jong et al., New England Journal of Medicine, Volume 353, December 2005, p 2667-2672). Therefore, there is a need in the art to develop new treatments capable of treating and / or improving the effects of avian influenza infection in subjects, including human and avian subjects. Viruses traditionally do not respond to antibiotic therapy. Therefore, other treatments are preferred when treating viral infections. One such therapy revolves around the use of protease inhibitors to interrupt the viral replication cycle. Protease inhibitor therapy has the potential to be used in the treatment of a wide range of diseases, including viral infections, such as those caused by retroviruses (e.g., HIV), hepadnaviruses (e.g., hepatitis viruses). C), herpesviruses (eg, herpes simplex virus and cytomegalovirus) and myxoviruses (eg, influenza viruses), as well as protozoan parasites (eg, Cryptospor id um and Plasmodium), in chemotherapy for the cancer and various pathological disorders. However, the protease inhibitors used in HAART have resulted in significant complications including lipodystrophy, hepatic failure and coronary artery disease. Accordingly, it would be a highly desirable advance in the art to provide improved compositions and methods for the treatment of viral infections that do not produce the undesirable side effects associated with known antiviral treatments. The inventors of the present application consider that the new compositions described herein are useful in the treatment and / or improvement of the effects of HIV infection and the H5N1 strain of avian influenza. The compositions of the invention may also be useful in the treatment of viral infections caused by other single-stranded RNA viruses and in the treatment of other diseases and medical conditions that induce the "cytokine crisis". The citation or identification of any document in this application does not consist in an admission that such document is available as a prior art with respect to the present invention. BRIEF DESCRIPTION OF THE INVENTION The present invention relates to novel compositions comprising therapeutically effective amounts of quercetin or one of its derivatives, an anti-convulsive component, such as phenytoin, with at least one calcium channel blocker component. (or metabolites thereof), a quinoline component, quinoline-quinone component or intermediates or derivatives such as chloroquine, in combination with a multivitamin component. The components combine and interact in ways that effectively treat viruses by reducing viral activity in infected subjects. Accordingly, an aspect of the present invention provides an antiviral composition comprising: (1) quercetin or one of its derivatives; (2) at least one calcium channel blocking component; (3) an anti-convulsive component; (4) a quinoline component or derivatives thereof; and (5) a multivitamin component; in sufficient amounts to treat and reduce viral activity in an infected subject. In another aspect of the invention, the weight ratio of the calcium channel blocker component to the quinoline component, to the anticonvulsant component is from about 100-240 mg to about 200-250 mg to about 100-300 mg. In yet another aspect of the invention, the components are in the form of particles and tablets with pharmaceutically acceptable carriers or tabletting agents. In another embodiment, the components are found in combination with a pharmaceutically acceptable liquid carrier. In addition, the composition may comprise about 100 to 240 mg of the calcium channel blocker component and about 200 to 250 mg of the quinoline component.

Another aspect of the present invention provides a method for reducing viral activity in an infected subject, comprising administering to the subject, a therapeutically effective amount of a composition comprising quercetin or one of its derivatives, at least one calcium channel blocker, an anti-convulsant, a quinoline or derivatives thereof, and multivitamins, in sufficient amounts to treat and reduce viral activity in the subject. In another aspect, there is provided a method for reducing viral activity in an infected subject comprising administering to the subject a therapeutically effective amount of the composition of the invention. In a preferred aspect, the invention provides methods for reducing viral activity in subjects infected with a coated single-stranded RNA virus, wherein the methods comprise administering to the subject a therapeutically effective amount of the composition of the invention. In another preferred embodiment, the invention provides methods for reducing immune activation and inflammation in subjects suffering from a medical condition or disease that induces a cytosine crisis, wherein the methods comprise administering to the subject a therapeutically effective amount of the composition of the invention. In further preferred embodiments the invention provides methods for reducing HIV activity in an HIV-infected subject comprising administering to the subject a therapeutically effective amount of the composition of the invention. In other preferred embodiments the invention provides methods for reducing the activity of the H5N1 avian influenza virus in infected subjects which comprises administering to the subject a therapeutically effective amount of the composition of the invention. In other aspects, the compositions of the present invention are administered in combination with the compositions described in the U.S. Patent. 6,262,019, the content of which is incorporated herein by reference. The compositions described in U.S. Patent: 6,262,019 raise the concentration of glutathione in cells and can be beneficially administered to patients infected by various viral infections, such as HIV or avian influenza, including the H5N1 strain of avian influenza. These - compositions are described as being a composition of interest, comprising a mixture of N-acetylcysteine; N-acetyl-d-glucosamine vitamin C by means of which the amount of vitamin C is in an amount of at least 1000 mg. or greater to facilitate the absorption of N-acetylcysteine through the cell membrane; and a pharmaceutically acceptable carrier for oral administration. Optionally, these compositions may also contain one or more of, alpha-lipoic acid, silmarin, quercetin, 1-glutamine, a probiotic, dietary protein or flavorings. Another aspect of the present invention provides a method for increasing glutathione levels in a virally infected subject, comprising administering to the subject a therapeutically effective amount of the composition comprising quercetin or one of its derivatives, at least one component of the channel blocker. of calcium, an anti-convulsant component, a quinoline component or derivatives thereof, and a multivitamin component, in amounts sufficient to increase glutathione levels in the subject. The components of quercetin, calcium channel blocker, anti-seizure and quinoline work synergistically with the multivitamin component to increase glutathione levels. The anti-convulsant (such as dilantin or phenytoin) together with the calcium channel blocker component (such as verapamil) "depresses" - the immune system decreasing the influx of calcium that leads to a decrease in phosphorylation Jak and Stat, thus decreasing the activation of the cell. The multivitamin component makes synergy with this, for example by decreasing the levels of glutathione and DHEA, which in turn decrease the oxidative stress, decreases interieucine 1 (IL1), interieucine 6 (IL6) and the production of tumor necrosis factor alpha (TNF alpha) that decreases viral activity. In another aspect, there is provided a method for increasing glutathione levels in a virally infected subject, comprising administering to the subject a therapeutically effective amount of the composition of the present invention in conjunction with the multivitamin component. It is further noted that the invention is not intended to encompass within the scope of the invention any product, process of product development or method to use the product, which meets the written description and qualification requirements of the USPTO (35 USC 112, first paragraph) or the EPO (Article 83 of the EPC), so that the applicant / s reserves the right and hereby submit a waiver on any product, method of making the product or process to use the product previously. described. These and other modalities are described and are - obvious or covered by the following Detailed Description. BRIEF DESCRIPTION OF THE DRAWINGS The following Detailed Description, given by way of example, but not proposed to limit the invention to the specific embodiments described, can be understood in conjunction with the attached Figures, incorporated herein by reference, in which : Figure 1 is a graph representing the results of 100 experiments on the effects of a composition according to the invention on viral load (measured by p24gag ICD) of peripheral blood lymphocytes infected with an HIV virus adapted in the laboratory (H9); Figure 2 is a graph depicting the results of 20 experiments on the effects of the compositions according to embodiments of the invention, on the viral load (measured by p24gag ICD) of peripheral blood lymphocytes infected with a strain isolated clinical viral highly active anti-retroviral therapy (HAART); and Figure 3 is a graph showing the effects of verapamil and quercetin on the CD4 count and the viral load of a hypertensive subject who refused anti-retroviral therapy. Figure 4 is a graph illustrating the effects of administration of the compositions described in the - Patent of E.U. 6,262,019, whose contents are incorporated herein by reference, on the levels of glutathione (GSH) in the lymphocytes of human patients infected with HIV, HCV or other viruses. Figure 5 is a graph illustrating the numbers of CD4 + cells detected using flow cytometry in cells that were labeled with anti-CD4 antibodies in samples from patients who had been treated with either HAART or PBS119. The treatment of peripheral blood mononuclear cells (PBMCs) with Nonidet P40 was used to remove PBS119 non-specifically bound before incubation with anti-CD4 antibodies. DETAILED DESCRIPTION OF THE INVENTION In this description, "comprises", "comprising", "containing" and "having" and the like may have the meaning attributed to them in the US Patent Law. and may mean "includes", "that includes", and the like; likewise "consisting essentially of" or "consisting essentially" have the meaning attributed to them in the US Patent Law. and the term is open allowing the presence of more meanings than those cited, as long as the new or basic characteristics of what is cited are not changed by the presence of more than what is cited, but excluding the modalities of the prior art.

- A "subject" in the context of the present invention can be a vertebrate, such as a mammal; more advantageously a human or a pet or domesticated or feed producer or producer feed or livestock or hunting or career or sport or laboratory such as murine, primates, cows, dogs, cats, goats, sheep, pigs or equines In addition, a "subject" in the context of the present invention may be an avian subject, such as, for example, poultry species. As used herein, the term "poultry" refers to those birds typically raised for the production of meat or eggs, such as chickens, turkeys, ducks or geese. Preferably, the subject is a human. An "infected subject" is a subject who has suffered from a viral infection or has been otherwise infected with a virus. A similar term used in the context of the present invention is "virally infected subject." It has surprisingly been shown that compositions comprising quercetin or one of its derivatives, anti-convulsants such as phenytoin, with blockers calcium channel (or metabolites thereof), quinoline, quinoline-quinone or intermediates or derivatives such as chloroquine in combination with multivitamins, they can be therapeutically effective in treating a viral infection. The present invention - also provides methods for decreasing viral activity and methods for increasing glutanone levels using the compositions of the invention when they are delivered to a subject in need thereof. The compositions and methods of the present invention can be advantageously used to inhibit viral diseases, such as, but not limited to, HIV, herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2)., varicella soster virus (herpes soster), smallpox virus, hepatitis A, B and C virus, cytomegalovirus, Epstein Barr, papilloma virus, viral influenza including avian influenza, in particular avian influenza of highly virulent H5N1 strain , viral parainfluenza, adenovirus, viral encephalitis, viral meningitis, arbovirus, arenavirus, picornavirus, coronavirus, and syncytial virus, among many other virus species. In addition, the compositions and methods of the invention could be used to treat parasitic diseases, such as, for example, malaria which is caused by protozoan parasites of the genus Plasmodium (including Plasmodium um falciparum, Plasmodium um vivax, Plasmodium ovale and Plasmodium um malaria). . The present invention described herein demonstrates that multivitamins, when supplied in combination with quercetin or one of its derivatives, an anti-convulsant such as phenytoin, a calcium channel blocker such as verapamil, and a quinoline, quinoline-quinone or intermediates or derivatives, can slow the progression of HIV to AIDS (Fawzi, W., et al., (2004) N.Engl. J. Med. 351: 23-32). Furthermore, decreased glutathione, present in a significant percentage of subjects afflicted by HIV, is an independent predictor of death by HIV: glutathione (GSH) is a frequent antioxidant in humans and reduces oxidative stress in HIV (Herzenberg, LA et al. al, (1997) Proc. Nati. Acad. Sci. EU 94; 1967-1972). The compositions and methods of the present invention substantially stop or prevent the reduction of glutathione, thus improving the quality of life and retarding viral progression in virally infected subjects. The compositions of the present invention can also be used in the treatment or amelioration of other viral infections, such as infection by avian influenza and other infections caused by single-stranded RNA viruses. In addition, the compositions of the present invention can also be used to reduce immune activation and a "cytosine crisis", as can be induced by a variety of other diseases and in a variety of disease states. For example, the compositions and methods of the present invention substantially reduce the inflammatory response in cells treated with a substitute for the highly pathogenic H5N1 strain of avian influenza.

- - The term "cytosine crisis" is well known in the art and refers to an excessively vigorous inflammatory response characterized by excessive production of pro-inflammatory cytokines such as interferons, interleukins and tumor necrosis factors. The induction of a cytosine crisis is a known feature of infection with the H5N1 strain of avian influenza (see, for example, ong et al., "Infections by avian influenza virus in humans" Chest, January 2006; Volume 129 (1), pages 156-68 and Yuen et al., "Human infection by H5N1 of avian influenza A" Medical Journal of Hong Kong, June 2005, Volume 11 (3), pages 189-99). In fact, it is believed that the cytosine crisis is one of the reasons for the severe symptoms and even for the mortality caused by H5N1 infection. In addition, the induction of a cytosine crisis has been reported in many other diseases, including diseases caused by pathogens such as viruses and bacteria, autoimmune diseases and cancer. (See, for example, Link et al., "The Cytosine Crisis in Multiple Sclerosis," Multiple Sclerosis, February 1998; 4 (1): 12-5; Makhija et al., "Cytosine Crisis in Acute Pancreatitis." of Hepatobiliary Pancreatic Surgery 2002; 9 (4): 401-10; Faulkner et al., "The mechanism of toxic shock mediated by superantigen: not a simple Thi cytosine crisis." Journal - Immunological November 15, 2005; 175 (10): 6870-7. In addition, the occurrence of a cytosine crisis after transplantation of an organ and other types of surgery has been noted (see, for example, Aikawa, N. "Cytosine crisis in the pathogenesis of multiple organ dysfunction syndrome associated with aggravations. Surgical "Nippon Geka Gakkai Zasshi 91 (9) - 111-111, 1996. The compositions of the present invention may be useful in the treatment of all such diseases and medical conditions characterized by an induction of a cytosine crisis. "low levels of glutathione" as used herein means a level of glutathione in the blood below 440 μg of glutathione / 1010 erythrocytes, as determined by the colorimetric method of Beutler et al., (Improved Method for Determination of Glutathione in the Blood, (1963) Journal of Clinical Medical Laboratory, 61: 882-8.) Normal levels in humans can range from about 440 to about 6. 54 μg of glutathione / 1010 erythrocytes. The inclusion of anticonvulsants including but not limited to carbamazepine, valproate, phenobarbital, primidone, etsuximide, gabapentin, lamotrigine, levetiracetam, tiagabine, topiramate, zonisamide and phenytoin (also known in the art as Dilantin) or derivatives thereof in compositions comprising a calcium channel blocker -, a quinoline, quinoline-quinone or derivatives thereof, and optionally, quercetin, may result in a absorption of Vitamin A and decreased Vitamin C (Tuchweber, B. et al., (1976) 100 (2): 100-5). Multivitamins, such as vitamins A and C, are important antioxidants that improve the function of phenytoin as an antiviral agent (Dubick, M.A. and Keen, C.L. (1985) Journal of Nutr. 115 (11): 1481-7). Additionally, quercetin promotes the conversion of β-carotene, present in the compositions of the present invention, to Vitamin A (Gomboeva, SB et al:, (1998) Biochemistry (Moscow) 63 (2): 185-90), which also improves the function of phenytoin. Anti-convulsants such as phenytoin, mephenytoin and ethotoin can be advantageously used in the compositions and methods of the present invention. Although phenytoin is described herein, any anti-convulsant can be used in the compositions and methods of the invention. Phenytoin sodium is a known antiepileptic compound. Phenytoin, phenytoin sodium, and processes for its manufacture are well known, see for example the U.S. Patent. No. 4,696,814; Patent of E.U. No. 4,642,316; and US Patent. No. 2,409,754, the contents of which are incorporated herein by reference. Phenytoin is a generic name for 5,5- diphenyl-2,4-imidazolidinedione. It is also known as diphenylhydantoin. It is used extensively to treat seizure disorders such as epilepsy. Because phenytoin is sparingly soluble in aqueous mixtures, it can not be effectively used in injectable solutions, or even in solid preparations for oral use. The compound is generally used as a sodium salt, which is rapidly soluble in water. Phenytoin sodium is commercially available as an extended release oral pharmaceutical composition. Phenytoin sodium is well known and is also referred to in the art as the monosodium salt of 5,5-diphenyl hydantoinate (phenytoin). Phenytoin sodium is commercially available in numerous polymorphic forms. In the context of the present invention, the phenytoin sodium incorporated in the present invention can be any commercially available polymorphic mixture. Any phenytoin salt can be used in the context of the present invention; the term "derivative (s) thereof" refers to any salt of phenytoin, hydrochlorides, malate, tartrates, maleates, succinates, chelates, among many other forms. Phenytoin salts are water-soluble whereas phenytoin is insoluble in water. The difference in solubility between the phenytoin salts and the - - Phenytoin is an important factor when preparing pharmaceutical preparations because the solubility will influence or dictate the types and amounts of other ingredients to be used in the pharmaceutical preparation. Phenytoin sodium is highly soluble-in-water. With regard to dosage levels, the anti-convulsant should be present in an amount corresponding to the adult human dosages generally recommended for a particular anti-convulsant. The specific dosage levels for anti-convulsants can be used herein as given, inter alia, in the "Medical Desk Reference," 1995 Edition (Medical Economic Data Production Company, Montvale, NJ) as well as in other reference works including "The Basis of Therapeutics" and "The Pharmaceutical Sciences of Remington" by Goodman and Gilman. Given the wide variation in the dosage level of the anti-convulsant, which depends largely on the specific anti-convulsant that is being delivered, there can similarly be a wide variation in the dosage level of the calcium channel blocker component, a component of quinoline, multivitamin component and quercetin component or derivatives thereof added to the composition to provide an antiviral effect. These amounts can be determined for a particular drug combination according to this invention - using routine experimental tests. Although the anti-convulsant component, the component of the calcium channel blocker, quinoline component, multivitamin component and quercetin component or derivatives thereof need not be supplied together, these must be present together in the subject at effective levels at the same time. weather. Although it is within the scope of the invention to separately administer the anti-seizure component, the calcium channel blocker component, the quinoline component or derivatives thereof, for convenience effect, it is preferred that these components are supplied in a unique dosage form. Multivitamins can serve as catalysts, photochemical initiators, nutritional supplements and auxiliary carriers. The multivitamin component may comprise one or more of the following: a water-soluble vitamin, a fat-soluble vitamin, vitamin A, vitamin B complex, (vitamin B complex), vitamin C, vitamin D, vitamin E, vitamin K , vitamin Bl, vitamin B2, vitamin B5, vitamin B6, vitamin B12, vitamin B15, niacinamide, folacin, folic acid, dehydroepiandrosterone (DHEA), ß-carotene, N-acetylcysteine, glucosaline, N-acetyl-D-glucosamine, silymarin , biotin, para-aminobenzoic acid (PABA), botaina, a-lipioco acid, - calcium, copper, magnesium, manganese, selenium (i.e., selenomethionine), zinc, boron, and chromium piconolate, but is not limited to these examples. In one embodiment of the invention, the multivitamin component comprises at least β-carotene, Vitamin C, Vitamin D, Vitamin E, N-acetylcysteine, glucosaline, N-acetyl-D-glucosamine, calcium, magnesium, boron, zinc, and piconolate. of chrome. Alkali transition metals and earth metals such as calcium can be administered as carbonate, citrate, ascorbate, pantothenate, phosphate or chloride salt. Similarly, zinc and magnesium can be administered as a carbonate, glycinate, phosphate, piconolate or chloride salt. A skilled artisan will consider providing for which vitamins are particularly suitable for inclusion in the compositions of the present invention, without undue experimentation. In one embodiment, the multivitamin component described herein as "Immune Vitality" is a tablet formulation comprising multivitamins in the following amounts. The compositions of the present invention may comprise the administration of Immuno Vitality, wherein the Immuno Vitality tablets can be added to the compositions described herein or taken simultaneously with the calcium channel blocker component, quinoline component, anti-seizure component and - optionally, quercetin component. In another embodiment of the invention, the multivitamin component, which may be Immuno Vitality, is supplied in the amount of four capsules by delivery of the antiviral compositions of the invention. Table 1: Components of Immunity Vitality - It has been determined that calcium channel blockers can have a positive treatment effect in subjects infected with AIDS. The in vitro effects of calcium channel blockers on HIV infection were studied both in HIV-adapted cell lines (HUT / H9) as well as in acutely infected peripheral blood lymphocytes. In addition, these experiments revealed a 50-60% reduction in HIV production (by detection of HIV RNA by the polymerase chain reaction) and ICD antigen p24gag at pharmacologically achievable concentrations. These results supported by other research on calcium channel blockers. The inhibition day influx of calcium (Ca2 +) during the activation of - - Cell blocking the regulated voltage Ca2 + channels can result in decreased symptoms in subjects suffering from overactive immune systems. It has also been shown that blocking the regulated voltage Ca2 + channel significantly reduces the debilitating symptoms in chronic fatigue and immunodeficiency syndrome (CFIDS). In addition, there was a concordant decrease in the activation of the T-cell without any change in the immuno-effect or mechanisms (i.e., cytotoxicity of the natural killer cell, IgG levels). This decreased activation involves decreased interieucine synthesis and decreased mitogenic reactivity. The addition of quinolines, such as quinoline-quinones, or intermediates thereof, such as chloroquine, has demonstrated synergistic effects when combined with calcium channel blockers, multivitamins, and anti-convulsants, as provided in the compositions herein invention. In one embodiment of the invention, the quinoline component comprises at least one member selected from the group consisting of chloroquinine, efloquinine, mefloquinine hydrochloride, primaquine, primaquine phosphate, carboxyprimagine and derivatives thereof. Chloroquine and its analogs, including hydroxychloroquine, have been shown to inhibit a variety of viral infections, as well as reduce immunoreactivity. Both effects are mediated by a change in the intracellular pH, which inhibits the viral, as well as the cellular enzymes involved in the activation. Hydroxychloroquine (HCQ), an antimalarial agent, can be used to treat subjects with autoimmune disease, and can suppress the replication of the immunodeficiency virus (HIV) in vi tro in the T-cells and monoliths by inhibiting the post-transcriptional modification of the virus. Chloroquine is an option drug for the treatment of acute malaria caused by the quinoline-sensitive strains. Chloroquine kills merozoites, thus reducing parasitaemia, but does not affect the hypnozoites of Plasmodium um vivax and Plasmodium ovals in the liver. These are eliminated by primaquine, which can be used in the treatment of malaria to prevent relapse. Chloroquine, which can be administered in solid or liquid form, combined with known pharmaceutically effective carriers, is a synthetic 4-aminoquinoline formulated as a phosphate salt for oral use and as a hydrochloride for parenteral use. The salts, hydrochlorides, tartrates, maleates, maleates, succinates, chelates and other forms of active ingredients described herein are incorporated in the term "derivatives". Therefore, the compositions according to the invention can include chloroquine and - derived from it. Chloroquine is rapidly and almost completely absorbed by the intestinal tract, reaches maximum plasma concentrations (50-65%) bound to protein in about 3 hours, and is rapidly distributed in the tissues. Because it is concentrated in the tissues, it has a very large apparent volume of distribution of approximately 13,000 L. From these places, it is released and metabolized slowly. The drug crosses the placenta quickly. It is excreted with urine with a half-life of 3-5 days. Increases renal excretion by acidifying the urine. Due to its large volume of distribution, a loading dose should be given when an effective squitocidal plasma level of chloroquine is urgently needed in the treatment of acute attacks. To avoid a life-threatening toxicity when chloroquine is given parenterally, it should be provided by a slow intravenous infusion or by small incremental doses intramuscularly. A therapeutically effective plasma concentration appears to be about 30 μg / L against P. vivax. Chloroquine is rapidly and completely absorbed after an oral supply. Usually 4 days of therapy are enough to cure the disease. The - drug concentrates in erythrocytes, liver, spleen, kidney and lung as well as in leukocytes. In this way, it has a large volume of distribution. It persists in erythrocytes. The drug also penetrates the central nervous system and crosses the placenta. Chloroquine is dealkylated by hepatic oxidases of mixed function, but some metabolic products retain anti-malarial activity. Both the mother drug and the metabolites are excreted predominantly in the urine. The proportion of excretion intensifies while the urine is acidified. Chloroquine is a highly effective blood schizontocide and is the 4-aminoquinoline drug that is most widely used in chemoprophylaxis and in the treatment of attacks by P. vivax, P. ovale, and other species of agents that cause malaria. Chloroquine is not active against pre-erythrocytic Plasmodium and does not eradicate P. vivax or P. ovale infections because it does not eliminate the persistent liver stages of those parasites. The exact mechanism of antimalarial action has not been determined. Chloroquine can act by blocking the enzymatic synthesis of DNA and RNA in both mammals and protozoal cells and forming a complex with DNA that prevents replication or transcription to RNA. Inside the parasite, the drug concentrates in the vacuoles and increases the pH of these organelles, interfering with the ability of the - - parasite metabolize and use hemoglobin. The drug can also decrease the synthesis of DNA in the parasite by disrupting the tertiary structure of the nucleic acid. The interference with the phospholipid metabolism inside the parasite depends on a chloroquine concentrating mechanism in the parasitized cells. The concentration of chloroquine in normal erythrocytes is 10-20 times more than in plasma; the parasitized erythrocytes, their concentration is approximately 25 times more than that in normal erythrocytes. Subjects usually tolerate chloroquine well when it is used in prophylaxis (including prolonged use) or treatment for malaria. Gastrointestinal symptoms, mild headache, pruritus, anorexia, malaise, blurred vision and hives are not unusual. Taking the drug after meals may reduce some adverse effects. Rare reactions include hemolysis in people with deficiency of glucose-6-phosphate dehydrogenase (G5PD), impaired hearing, confusion, psychosis, seizures, blood dyscrasia, skin reactions, alopecia, hair discoloration and hypotension. Chloroquine is contraindicated in subjects with a history of liver damage, alcoholism, or neurological or hematological disorders. Certain antacids and agents - - Anti-diarrhea (kaolin, calcium carbonate and magnesium trisilicate) may interfere with the absorption of chloroquine and should not be taken during approximately 4 hours after day administration of chloroquine. Quinine, a bitter-tasting alkaloid, is rapidly absorbed, reaches peak plasma levels in 1-3 hours and is widely distributed in body tissues. Approximately 80% of the plasma quinine is bound to protein; The red blood cell levels are approximately 20% of the plasma level and the cerebrospinal fluid concentrations of approximately 7%. The elimination of half-life of quinine is 7-12 hours in normal people but 8-21 hours in people infected with malaria in proportion to the severity of the disease. Approximately 80% of the drug is metabolized in the liver and is excreted mostly in the urine. Excretion accelerates in acid urine. With constant daily doses, plasma concentrations usually reach a plate on the third day. In a normal or light infection, standard oral doses result in levels of approximately 7 μm / mL; in severe malaria, higher plasma levels are reached. A poor concentration of plasma of more than approximately 5 μm / mL is effective to eliminate the asexual parasites of P. vivax malaria and a - -somewhat higher concentration for P. falciparum malaria. Concentrations lower than 2 μm / mL have little effect, while concentrations of more than 7 μm / mL are usually accompanied by adverse reactions of "cinchonismo". Due to the narrow therapeutic range of approximately 2-7 μm / mL, adverse reactions are common during treatment with quinine for P. falciparum malaria. Quinine acts quickly, is a highly effective blood schizontocide against four malaria parasites. The drug is gametocidal for P. vivax and P. ovale, but it is not very effective against the gametocytes of P. falciparum. Quinine has no effect on the sporozoites or the liver stages of any of the parasites. The molecular mechanism of the drug is not clear. It is known that quinine depresses many enzyme systems. It also forms a hydrogen-linked complex with double strand DNA that inhibits strand separation, transcription and protein synthesis. Mefloquine is used in the prophylaxis and treatment of P. falciparum malaria resistant to chloroquine and resistant to multidrug. It is also effective in prophylaxis against P. vivax and presumably against P. ovale and P. malaria. Mefloquine hydrochloride is a synthetic methanol derivative of 4-quinoline chemically - related to quinine. It is usually given orally only due to the intense local irritation that can occur with parenteral use. It is well absorbed, and the peak plasma concentration is reached in 7-24 hours. A single oral dose of 250 mg of salt results in a plasma concentration of 290-340 ng / mL, while the continuation of this dose daily results in poor permanent plasma concentrations of 560-1250 ng / mL. Plasma levels of 200-300 ng / mL may be necessary to achieve chemo-suppression in P. falciparum infections. The drug is highly bound to plasma proteins, concentrated in red blood cells, and extensively distributed in tissues, including the central nervous system. Mefloquine dissipates in the liver. Its acid metabolites are excreted slowly, mainly with faeces. Its elimination half-life, which varies from 13 days to 33 days, tends to be shortened in subjects with acute malaria. The drug can be detected in the blood for months after the cessation of dosing. Primaquine phosphate is a synthetic derivative of 8-aminoquinoline. After oral administration, the drug is usually absorbed well, reaching peak plasma levels in 1-2 hours and then it is almost completely metabolized and excreted in the urine. The average life of - Primaquine plasma is 3-8 hours and its peak serum concentration is 50-66 ng / mL; amounts of trace in tissues but only a small amount binds in them. Its major metabolite is a derivative deaminatado, carboxiprimaquina, which reaches plasma concentrations more than ten times greater than those of the parent compound, is slowly eliminated (half-life of 22-30 hours), and accumulates with daily dosage; Peak serum concentrations after 14 daily doses are 432-1240 ng / mL. It has not been determined whether primaquine or one of its metabolites is the active compound. The mechanism of the antimalarial action of the primoquina is not well understood. The quinoline-quinone intermediates derived from primaquine are redox electron carrier compounds that can act as oxidants. It is thought that these intermediaries produce most of the hemolysis and methemoglobinemia associated with the use of primaquine. Quercetin [2- (3,4-Dihydroxyphenyl) -3,5,7-trihydroxy-4H-1-bensopyran-4-one] and derivatives thereof are a natural flavonoid and are used for their ability to eliminate toxic compounds found in the liver. It has anti-hepatotoxic, antiviral, anti-inflammatory and antibacterial properties and has the structural formula represented below: wherein R1, R2, R3, R4 and R5 are hydrogen. Quercetin derivatives include but are not limited to compounds wherein one or more of R 1, R 2, R 3, R 4 and R 5 acyl, alkoxy, glycosyl or combinations thereof. In one embodiment of the invention, the acyl includes but is not limited to C 1 -C 4 acyl. In another embodiment of acyl, the acyl is acetyl. In one embodiment of the invention, alkoxy includes but is not limited to C1-C4 alkoxy, phenylalkoxy or benzylalkoxy. In yet another embodiment of the invention, glycosyl includes but is not limited to, alosyl, altrosyl, glucosyl, mannosyl, gulosyl, idosyl, galactosyl or talosyl. In another glycosyl embodiment, the glycosyl is glucosyl or galactosyl. The quercetin derivatives also include compounds wherein the quercetin rings have additional hydroxy moieties which in turn can be derived as described above. In one embodiment of this quercetin derivative, an additional hydroxy group is - found in position 6 of the benzopyran ring (also known as corcetagetin). Quercetin can be synthesized by the method of Shakhova, I.K. et al. , (1962) Zh. Obsheh Khim. 32: 390, incorporated by reference. Quercetin can inhibit HIV binding to CD4 receptors in host cells, as well as the inhibition of both viral integrase and reversed viral transcriptase, and has also been shown to inhibit HIV activity. Example 8 of the present application provides data demonstrating the ability of compositions comprising quercetin to bind to CD4 + T cells in HIV-infected patients. It is believed that the efficacy of the compositions of the present invention against other viral diseases, such as avian influenza and in particular the H5N1 strain of avian influenza, can be mediated, at least in part, by the binding of quercetin to the surface of the cells thus preventing the viruses from joining these cells. For example, it is believed that compositions of the present invention comprising quercetin may also bind to / block epithelial cells thereby blocking the binding of avian influenza viruses. It is also believed that the compositions of the present invention comprising quercetin may have antiviral effects against other viral diseases by binding to / blocking the cells usually infected by - - that virus. For example, it is believed that the binding / blocking of hepatocytes by quercetin can block or inhibit the binding of Hepatitis C virus. Quercetin is a naturally occurring flavone, frequently found in plant material consumed by animals, including humans, daily. Quercetin, a common constituent of the plants, was identified from an extract of traditional Chinese medicine (TCM) which was determined to be an aryl hydrocarbon receptor (Ah) antagonist. The chemical configuration of quercetin, like flavones in general, is composed of two benzene rings linked through a heterocyclic pyrin ring. Quercetin has been shown to be a genotoxic compound that can initiate carcinogenic activity in certain tissues if it is supplied in high doses for a prolonged period, (Dunnick, JK, and Hailey, JR (1992), Fundam. Appl. Toxicol. 19 (3 ): 423-31). It has been shown that when in the presence of transformed cancer cells, quercetin has an anti-proliferative effect on those transformed cancer cells. (Scambia, G. et al., (1993) Int. J. Cancer 54 (3): 462-6). Quercetin derivatives can be isolated either from natural products or can be synthesized from quercetin using known synthetic techniques - by those skilled in the art (e.g., Protecting Groups in Organic Non-Theses, Third Edition, editors Greene &Wuts, John Wiley &Sons, Inc., 1999 - Chapter 2 Protection for the Hydroxyl Group, Including 1 , 2- and 1,3-Diols - pages 23-148 (Ethers) and pages 149-200 (Esters); Chemistry of Carbohydra to Prepara tive, ed. Stephen Hanessian, Marcel Dekker, Inc., 1996 - Chapter 3 - Chemical Synthesis of O- and N-glycosyl compounds and oligosaccharides). It has been reported that phentoin decreases the levels of dehydroepiandrosterone (DHEA) (Levesque, LA et al., (1986) Journal of Clinical Endocrinological Metabolism 63 (l): 243-5) and GSH (Ono, H. et al., (2000), Clin. Chim. Acta 298 (1-2): 135-43), resulting in an increased cortisol / DHEA ratio in epileptic subjects (Ono, H. et al., (3000) Chim. Acta 298 (1-2): 135-43; Gallagher, EP and Sheehy, KM, (2001) Toxicology Sciences 59: 118-126), which is associated with increased lipodystrophy, even in the absence of anti-retroviral therapy (ART) (Shevitz, A. et al., (2001) AIDS 15 (15): 1917-30; Kotler, DP: § (2003) AIDS Read. 13 (4 Suppl): S5-9). It has also been reported that DHEA levels decrease the quality of life in an advanced HIV (Piketty, C. et al., (2001) Endocrinological Clinic. (Oxford) 55 (3): 325-30). A decrease in KHEA is further associated with decreased levels of CD4 (de la Torre, G. et al., (1997) Clin. Exp. Rheumatol. 15 (l): 87-90) and loads - - HIV viruses increased (Christeff N. et al., (1999) Nutrition 15 (7-8): 534-9). Increased HIV activity associated with decreased DHEA has been linked to an increase in the production of interleukin-6 (IL-6) (Centurelli, MA and Abate, MaA. (1997) Ann.Pharmacother. 31 (5): 639 -42) and a decrease in the production of IL-2, a hallmark of HIV / AIDS progression (Ferrando, SJ et al., (1999) J. Acquir. Im une Defic. Syndr. 22 (2): 146 -54; Yang, JY et al., (1993) AIDS Res. Hum. Retroviruses 9 (8): 747-54). Increases in IL-6 production subsequently increase HIV activity as well as increases pro-inflammatory decitosin IL-1 levels and tumor necrosis factor-a (TNF), which allows the reactivation of latent HIV in cells. Without wishing to be bound by any theory, it is believed that the present composition and methods described herein decrease IL-1, TNTa, and the secretion of IL-6 and prevent the over-regulation of the long terminal repeater reporter gene required for activation of latent HIV Christeff, N. et al. , (2000) Ann. NY Acad. Sci. 917: 962-70). A high cortisol / DHEA ratio is also associated with weight loss in HIV (Christeff, N. et al., (1997) Psychoneuroendocrinology 22 Suppl 1: Sll-18; Ono, H. et al., (2000) Clin Chim. Acta 298 (1-2): 135-43). In addition, the use of phenytoin decreases the absorption of Zn2 +, Cu2 + and Mg2 + and the production of reduced glutathione - - (Wells, P.G., et al., (1997) Mutat. Res. 396 (1-2): 65-78). The reduction in GSH production can also be reversed by quercetin, which increases 50% GSH production (Myhrstad, MC et al., (2002) 32 (5): 386-93) by stimulating the downstream events that promote the production of GSH (Fiorani, M. et al., (2001) Free Radie, Res. 34 (6): 639-48). It has been reported that reduced glutathione is an independent predictor of death in late-stage HIV / AIDS subjects (Herzeberg, LA et al., (1997) Proc. Nati. Acad. Sci. United States of America 94: 1967-1972) . The reasons for this are varied, but include a decrease in GSH levels, ultimately resulting in increased oxidative stress in HIV. An object of the present invention provides a method for increasing glutathione levels in virally infected subjects, comprising administering a therapeutically effective amount of the compositions of the present invention. Oxidative stress can be aggravated by decreasing Vitamin A, C and DHEA in subjects taking phenytoin (Dubick, MA and Keen, CL (1985) J. Nutr 115 (11: 1481-7; Ono, H. et al. , (2000) Clin. Chim. Acta 298 (1-2): 135-43) It also results in increased apoptosis of non-HIV infected CD4 + T cells (Fiorani, M. et al., (2001) Free Radie. Res. 34 (6): 639-48.) Apoptosis of CD4 + cells is also decreased by quercetin which is protected from oxidation by vitamin C (Vrijsen, R. et al., (1988) J. Gen. Virol 69: 1749-51) The importance of decreased accelerated apoptosis reported in HIV has been demonstrated in the art, which describes that corticosteroids decrease apoptosis and increase CD4 counts in HIV without a significant increase in HIV viral activity (Yang, JY et al., (1993) AIDS Res. Hum. Retroviruses 9 (8): 747-54; Christeff, N. et al., (2000) Ann. NY Acad. Sci. 917: 962-70. In addition, the presence of multivitamins, such as N-acetylcysteine, glucosaline and Vitamin C protects quercetin from oxidation and enhances its anti-HIV function through an increased production of GSH (Myhrstad, M. C. et al. , (2002) Free Radie. Bio. Med. 32 (5): 396-93; Jan, C. Y. et al. , (1991) Biochim. Biophys. Acta 1086 (1): 7-14). GSH also reduces the teratogenicity associated with the administration of phenytoin (Wells, PG, et al., (1997) Mutat, Re. 396 (1-2): 65-78) and prevents phenytoin from becoming a free radical induced. by the P450 system of hepatic cytochrome (Jan, CY et al., (1991) Biochim, Biophys, Acta 1086 (1): 7-14). This can reduce the accelerated metabolism of many drugs by phenytoin by decreasing the increased activation of phenytoin in the P450 system of the hepatic cytochrome. In addition, glutathione (GSH) restores the - Electrophysiological impairment of neuromuscular function associated with phenytoin (Raya, A. et al., (1995) Free Radie, Biol. Med. 19 (5): 665-7) and is not expected to contribute to peripheral neuropathy associated with HIV infection. Vitamin K (Raya, A. et al., (1995) Free Radie.

Biol. Med. 19 (5): 665-7) is another multivitamin subject to oxidation and is therefore prone to the production of free radicals associated with increased HIV activity. This oxidation can be prevented by Vitamin C (Myhrstad, M.C. et al., (2002) Free Radie. Bio.

Med. 32 (5): 396-93; Boots, A. W. et al. , (2003) Biochem.

Biophys. Res. Commun. 308 (3): 560-5; Kubow, S. and Wells, P. G. (1989) Mol. Pharmacol. 35 (4): 504-11), which also protects quercetin from oxidation. Quercetin has multiple functions, including, but not necessarily limited to, protection against endothelial cell dysfunction (Centurelli, M.A. and Abate, M.A., (1997) Ann. Pharmacother. 31 (5): 630-42; Nooroozi, M. et al. , (1988) Am. J. Clin. Nutr. 67 (6): 1210-8) induced by insulin resistance that has been reported in HIV infection without antiretroviral therapy (Shevitz, A. et al., (2001) AIDS 15 (15: 1917-30), but only if it is protected from oxidation, quercetin not only increases GSH production, but also reduces lipid peroxidation, which is the major source of oxidative stress and increases HIV activity.

(Su, JF et al., (2003) Biomed, Environ. Sci. 16 (1): 1-8), both systematically and in the Gl tract, a greater reserve of HIV infection (Washington, CB et al., ( 1998) J. Acquir, Immune Defic, Syndr, Hum, Retrovirol, (19 (3): 203-9, Kotler, DP (1989) Adv. Intern, Mde.34: 43-71.) GSH and quercetin can restore the normal gastrointestinal antioxidant status in 7 days (Galvez, J. et al., (1994) Gen. Pharmacol 25 (6): 1237-43) In addition, GSH and quercetin improve the antioxidant status of the liver by increasing the glutathione production that is important in subjects co-infected with hepatitis C and / or B (Molina, MF et al., (2003) Biol. Pharm. Bull. 26 (10): 1398-1402) when protected from oxidation by Vitamin C. In addition, quercetin, when protected from oxidation, decreases DNA strand breaks in activated lymphocytes which has been reported, results in decreased CD4 + and CD8 + T-cell function, lymph death increased cytosis and increased HIV activity (Noroozi, M. et al. , (1998) Am. J. Clin. Nutr. 67 (6): 1210-8; Szeto, Y. T. and Benzoe, I. F., (2002) Free Radie. Res. 36 (1): 113-8). Vitamins C, B6 GSH protect skin sensory neurons, which can be damaged by phenytoin and, as noted previously for GSH, can mitigate peripheral neuropathy associated with HIV infection (Wells, PG et al., (1997 Mutat Res 396 (1-2): 65-78).

- - It has also been reported that quercetin decreases the absorption of Vitamin C (Fiorani, M. et al., (2001) Free Radie, Res. 34 (6): 1749-51; Vrijsen, R. et al., (1988 ) J. Gen. Virol. 69 (Pt. 7) 1749-51), which in turn is required to avoid the oxidation of quercetin, as well as reduce the absorption of Vitamin E (Jan, CY et al., (1991) Biochim, Biophys, Acta 1086 (1): 7-14). This is avoided by the compositions of the present invention and is particularly important since Vitamin C and Vitamin E both regenerate the reduced GSH after oxidation, a process that would otherwise be inhibited by reducing the activity of glutathione reductase ( Mak, S. et al., (2002) Am. J. Physiol. Herat Cir. Physiol. 282: H2414-H2421; Noroozi, M. et al., (1998) Am. J. Clin. Nutr. 67 (6 ): 1210-8) and, if protected by Vitamins C and E, would promote the oxidation of GSH and loss of its antioxidant functions. Quercetin (Hu, HL et al., (2000) Mech. Aging Dev. 121 (1-3): 217-30) has also been shown to decrease aberrant B cell function in HIV as well as decrease endothelial dysfunction when protected of oxidation by Vitamin C & E, which is important since endothelial dysfunction is associated with insulin resistance (Fiorani, M. et al., (2001) 34 (6): 639-48) and 35% of subjects with HIV, even without ART, they have a tolerance to impaired glucose (Shevitz, A. et al., (2001) AIDS 15 - - (15) .1917-30; Kotler, K. P. (2003) AIDS Read. 13 (4 Suppl): S5-S9). In addition, it has been reported that diabetic neuropathy decreases (Anjaneyulu, M. and Chopra, K. (2004) Clin. Exp. Pharmacol. Physiol. 31 (4): 244-248; Coldiron, AD Jr., Et al., (2002) J. Biochem Mol. Toxicol 16 (4): 197-202) and is believed to protect against neuropathy of HIV. Furthermore, quercetin is well absorbed in the jejunum (66%) (44), while the rest is excreted. The return to a normal oxidative status in the gastrointestinal tract (a greater reserve of HIV) after 7 days (Myhrstad, MC et al., (2002) Free Radie. Biol. Med. 32 (5): 386-93; Galvez , J. et al., (1994) Gen Pharmacol 25 (6): 1237-43) in animals treated with quercetin can be explained, in part, due to the increase in GSH levels induced by quercetin. Quercetin can also decrease glucose uptake (Song, J. et al., (2002) J. Biol. Chem. 277 (18): 15252-60) if it is protected from oxidation by Vitamin C, and can synergize with the effect of phenytoin (Cudworth, AG and Barber, HE, (1975) Eur. J. Pharmacol. 31 (l): 23-8), which decreases the release of insulin from the pancreas (Fuenmayor, NT, et al. , (1997) J. Cardiovasc Pharmacol 30 (4): 523-7). In addition, the presence of a calcium channel blocker, such as verapamil, increases insulin sensitivity. Together these components function to protect, at least partially, against insulin resistance, impaired glucose tolerance (Wahl, MA et al., (1998) Esp. Clin Endocrinol. Diabetes 106 (3): 173- 7) and results in increased endothelial dysfunction and cardiovascular events (Mak, IT et al., (1995) Biochem Pharmacol 50 (9): 1531-4) in HIV reported even in the absence of ART (Shevitz, A et al., (2001) AIDS 15 (15): 1917-30; Kotler, DP (2003) AIDS Read. 13 (4Suppl): S5-S9). In addition, a number of components comprising the compositions of the present invention reinforce or are additive / synergistic for the mechanism mentioned herein. These include, but are not limited to, replacement of Mg2 + and Zn2 +, which are diminished by phenytoin (Wells, P. G. et al., (1997) Mutat, Res. 396 (1-2): 65-78). Mg2 + decreases the nuclear factor? B (NF-KB), IL-1, IL-6 and tumor necrosis factor-a (TNF-a) production and excretion, which together with Verapamil (Yokohama, T. et al., (2003 ) Life Sci. 72 (110: 1247-57) and DHEA, decrease HIV activity as well as protect against endothelial dysfunction (Shogi, T. et al., (2003) Magnes. Res. 16 (2): 111- 9) Endothelial dysfunction may be associated with insulin resistance and increased cardiovascular events by decreasing oxidative stress (Rubio-Luengo, MA et al., (1995) Am. J. Hypertens. 8 (7): 689-695) The addition of Ca 2+, Mg 2+, borone and Vitamin D in the compositions of the present invention may also protect against bone loss associated with long-term use of phenytoin and which occurs in HIV even in the absence of ART (Shevitz , A. et al., (2001) AIDS 15 (15): 1917-30) In addition, the chromium piconolate in the inventive compositions of the invention can increase insulin activity. ina through interaction with insulin receptors on the surface of the cell (Kims, D. S. et al. , (2002) Metabolism 51 (5): 589-94) and increases the GLUT-4 glucose transporter translocation required to maximize insulin activity (Cefalu, WT et al., (2002) J. Nutr. 132 ( 6): 1107-14). Moreover, by reducing insulin resistance by the additive or synergistic mechanism described herein, endothelial dysfunction is reduced, triglyceride levels are lowered and platelet aggregation is decreased (Diabetes Educ. (2004) Suppl: 2-14 ). The addition of chromium can inhibit reactive oxidative stress by improving insulin function and improving or reinforcing immune function (Shrivastava, R. et al., (2002) FEMS Immunol.Med. Microbiol. 34 (1): 1-7 ) while the Zn2 + in the compositions of the invention has additive effects in the decrease of insulin resistance, low density lipoprotein levels, which decrease atherogenesis and increase the cardiovascular and cerebral aberrations that have been reported in HIV / AIDS even in absence - from ART (Shevitz, A. et al., (2001) AIDS 15 (15): 1917-30; Kotler, D. P. (2003) AIDS Real. 13 (4 Suppl) _S5-S9). Verapamil has a number of other functions that include anti-HIV activity, as well as reducing some of the metabolic dysfunctions that are a required part of HIV infection. It also avoids the biliary excretion of Vitamin E (Mustacich, DJ et al., (1998) Arch. Biochem. Biophys. 350 (2): 183-92), which is required to replenish the reduced glutathione and restores the sensitivity of the parasite. Plasmodium um falciparum malaria to chloroquine therapy by blocking the multidrug resistance pump, the P-glycoprotein (Vezmar, M. and George, E. (1998) Biochem.

Pharmacol. 56 (6): 733-42; Siddiqi, N. J. and Alhomida, A. S. (1999) In Vivo 13 (6): 547-50). This restoration of sensitivity can be increased by both DHEA and glutathione (Freilich, D. et al., (2000) Am. J. Trop. Med. Hyg. 63 (5-6): 280-3). This restoration is particularly advantageous since it decreases the increased oxidative stress in the African population infected by various forms of malaria and additionally co-infected with HIV which, if left untreated, can result in anemia and an obligatory increase in oxidative stress. as a progression of HIV. Decreased oxidative stress in subjects coinfected with HIV and malaria can also be further reduced by the inclusion or supply of Vitamins - - A, C and E, which both reduce malaria (Farombi, E. 0. et al., (2003) Drug Chem. Toxicol.26 (l): 21-6) and HIV (Fawzi, WW et al. , (2004) N. Engl. J. Med. 351: 23-32). Chloroquine, especially in high doses (> 2250 mg per day; PDR Volume # 59, page 2984) or used over a prolonged period may result in liver, kidney and retinal toxicity. The -lipoic acid is another multivitamin component that can be included in the compositions and methods of the present invention. A-lipoic acid protects against liver toxicity (Pari, L. and Murugavel, P. (2004) J. Appl. Toxicol.24 (l): 21-6; Murugavel, P. and Pari, L. (2004) Ren. Fail. 26 (5): 517-24) and renal (Toler, SM (2004) Exp. Biol Med. (Maywood) 229 (7): 607-15) associated with long-term or high-dose use of chloroquine, although Vitamin C, E, GSH and other antioxidants in the compositions of the invention described herein protect against chloroquine-induced retinopathy caused by increased oxidative stress (Dale, MM and Ladd, R. (1984) Br J. Pharmacol. 83 (1): 293-8). This is particularly significant since chloroquine increases the lysosomal pH, thus decreasing lymphocyte activation and HIV activity (Choo, E.F. et al., (2000) Drug Metab.Date 28 (6): 655-660). This function and the decrease reported in the outbreak of certain herpesviruses - by chloroquine, which has been reported to increase the replication of HIV from the latter in part by increasing the production and excretion of IL-6 (Washington, CB et al., (1998) J. Acquir. Immune Defic. Syndr. Hum. Retrovirol 19 (3): 203-9; Mocroft, A. et al., (1999) AIDS 13 (8): 943-50) act together to reduce the production and excretion of IL-6 and the required decrease in HIV replication. These mechanisms are reinforced by the function in DHEA, which also decreases the production of IL-1, IL-6 and TNF (Meierjohann, S. et al., (2002) Biochem. J. 368 (Pt. 3): 761 -8; Mak, IT et al., (1994) Am. J. Physiol. 267 (5Pt.l): C1366-70; Magwere, T. et al., (1997) free Radie. Biol. Med. 22 ( 1-2): 321-7, Abdel-Gayoum, AA et al., (1992) Pharmacol, Toxicol 71 (3 Pt.l): 161-4). In addition to its role as an HIV replication writer, chloroquine has a number of other functions. In African populations with a high frequency of malaria and obligate anemia arising from malaria infection, it is an independent predictor of HIV progression (Belperio, PS and Rhew, DC (2004) Am. J. Med. 116 Suppl. 7A: 27S-43S) and ultimately decreases the quality of life. Treatment with chloroquine with or without the conversion of resistant malaria by verapamil (Vezmar, M. and George, E. (1988) Biochem Pharmacol 56 (6): 733-42; Siddiqi, NJ and Alhomida, AS (1999) In Vivo 13 (6): 547-50), when supplied with DHEA and GSH (Safeukui, I. et al., (3004) Biochem.Pharmacol. 68 (10): 1903-10), can reverse anemia and restore GSH levels. Similarly, the activity of chloroquine can be increased by the GSH (Galvez, J. et al., (1994) Gen. Pharmacol. 25 (6): 1237-43) by decreasing the oxidative stress noted in the Mg2 + deficiency and the infection alarming that is common in HIV (Herzenberg, LA et al., (1997) Proc. Nati. Acad. Sci. EU 94: 1967-1972; Tuchweber, B. et al. , (1976) Arch. Pathol. Lab. Med. 100 (2): 100-5) and replaced by IV. Furthermore, it has been reported that long-term use of chloroquine in animal studies reduces GSH and selenium levels (Herzenberg, LA et al., (1997) Proc. Nati. Acad. Sci. EU 94: 1967-1972) . This is important since a GSH and reduced selenium levels (Herzenberg, L. A. et al., (1997) Proc. Nati. Acad. Sci. E.U. 94: 1967-1972) increase the activity and progression of HIV. This potential effect can be prevented by the components comprising the compositions of the present invention. The compositions of interest, according to the preferred embodiments of the invention, may comprise in a mixture: quercetin or one of its derivatives, an anti-convulsant component, at least one calcium channel blocking component; a quinoline component, a multivitamin component; derivatives of these components, such as - - pharmaceutically acceptable salts, hydrochlorides, tartrates, maleates, maleates, chelates and metabolites thereof and a pharmaceutically acceptable systemic carrier for oral administration. The invention also comprises a combination of the metabolites of these components. The components can be provided in solid or liquid form, such as suspensions of particles or in solutions based on water or alcohol. The compositions may be formulated for oral, topical, intrathecal, intramuscular, subcutaneous, epicutaneous, intranasal, nebulizer, or parenteral delivery, although oral administration is preferred. The components of the composition should be provided in therapeutically effective amounts to treat viruses, such as HIV. At a weight ratio of approximately 100-240 mg Ca2 + channel blocker (or metabolite): approximately 200-250 mg of chloroquine, quinoline, quinoline / quinone: approximately 100-300 mg of anti-convulsant: and approximately 1200-2400 mg of quercetin. The invention also comprises the administration of a composition according to the preferred embodiments of the invention, to a mammal suffering from viral infection such as HIV, in a dose sufficient to reduce and treat such infection. It has been shown that the inhibition of calcium influx (Ca2 +) during the activation of the cell by blocking regulated voltage Ca2 + channels, results in decreased symptoms in subjects suffering from hyperactive immune systems. This decreased activation involves decreased interieucine synthesis and decreased mitogen reactivity. The in vitro study of the effect of Ca2 + channel blockers on HIV infection in both HIV-adapted cell lines (HUT / H9) as well as in acutely infected peripheral blood lymphocytes revealed a 50-60% reduction in the production of HIV (HIV PCR RNA) and an ICD antigen p24gag in pharmacologically feasible concentrations. We sought a second, non-competitive complementary class of drugs that would provide an additive or resultant synergistic effect. In experiments similar to those described above, the addition of effective amounts of chloroquine to both cells infected with H4T or peripherally infected peripheral blood mononuclear cells.

(PBMC), reduced viral activity (replication) of 20-40%. In similar cultures with pharmaceutically feasible concentrations of verapamil, a calcium blocker and chloroquine, viral activity was reduced by 75-85%. Therefore, in conjunction with the Ca2 + channel blocker, the net effect is to reduce the activation of NF-? B from the cell as well as the HIVTAT motor and suspend the virus discovered in - - the hostile environment of the cytosol. It has been demonstrated in multiple studies that the non-translated, non-integrated virus is very susceptible to degradation and the more the virus is kept in this vulnerable state, the less competent it becomes for replication. In experiments similar to those described above, a standardized quercetin extract (containing 1-10 μg / ml of quercetin available with Sigma Aldrich) revealed a 5-20% reduction in HIV activity. When added to preferred concentrations (30 μg / ml of verapamil and 10 μg / ml of chloroquine) the composition achieved an 85-95% reduction in HIV activity. It is believed that quercetin decreases viral activity by weakly inhibiting CD4 binding as well as the conversion of RNA to DNA, preventing the integration of viral DNA into the genome. This occurred in a non-cytotoxic manner with in vi tro concentrations, which are easily achieved in vivo and which result in at least a decrease of two logarithms in viral activity. This is a larger decrease compared to current HIV drugs such as AZT, D4T, DDI, where viral activity decreases by 0.4-0.7 log. This finding of significant interaction between Ca2 + channel blockers and chloroquine and its analogues as well as the benign secondary effect profile of - Quercetin represents a safe, potentially effective, and economical alternative to current HIV therapy for the more than 40,000,000 afflicted individuals around the world who can not afford current HAART therapy. Initial studies in adults indicate that the following proportion for dosage units for each of the ingredients would be appropriate. Phenytoin 100-300 mg Verapamil 5-500 mg, preferably 100-240 mg Chloroquine 200-250 mg Quercetin 1200-2400 mg Multivitamin four capsules of Immuno Vitality or equivalent composition These dosages should be administered 1-4 times per day, preferably once per day. It is also considered that lower dosages may be appropriate for children. The adjustment of the dosages according to body weight and metabolism should be apparent to those skilled in the art. The compositions including the active ingredients listed above may be effective in reducing viral activity in mammals. It is preferred that each component be present in a weight ratio of 100 to 240 mg of Ca2 + channel blocker at about 200 to 250 mg. of quinoline, quinoline / quinone or intermediate at approximately 1200-2400 mg of quercetin. As used herein, the identification of a drug or other therapeutic compound is conceived to also refer to pharmaceutically effective forms of the drug, such as salt forms, hydrochlorides, tartrates, maleates, maleates, succinates, chelates and so forth to establish a sustained release of one or more of the active ingredients, which are used in the administration of the drug. Any suitable antagonist, generally of neuronal dependent voltage Ca2 + channels, can be effective under certain conditions. In one embodiment of the invention, calcium channel antagonists include, but are not limited to, drugs that are capable of crossing the blood barrier of the brain, e.g., nimodipine (Miles Pharmaceuticals, West Haven, CT), Smith Kline drug No. 9512 (Smith Kline, French-Beecham, Philadelphia, PA), and diproteverin (Smith Kline, French-Beecham). In another embodiment of the invention, calcium channel blockers are antagonists that are less permeable to CNS, for example, verapamil (Calan, GD Searle &Co., Chicago, 111; Isoptin, Knoll, Whippany, NJ), nitrendipine and diltiazem (Cardizem, Marion, Kansas City, Mo). Other Ca2 + channel antagonists that may be useful are myoflazine, flunarizine, bepridyl, lidoflazine, CERM-196, R-58735, R- - - 56865, ranolazinam nisoldipine, nicardipine, PN200-110, felodipine, amlodipine, R- (-) -202-791, and R - (+) Bay K-8644 (Miles, Bayer) or derivatives thereof, whose chemical formulas are describe in Boddeke et al. , Pharm trains. Sci. (1989) 10: 397 and Triggle et al. , Pharm trains. Sci. (1989) 10: 370, incorporated by reference. Verapamil is known as a Ca2 + channel blocker and is a competitive inhibitor of P-glycoprotein, as described by Inoue et al. , (1993) J. Biol. Chem, 268 (8): 5894-8; Hunter, J. et al. , (1993) Pharm ,. Res. 10 (5): 743-9; Hori, R. et al. , (1993) J. Pharmacol. Exp. Ther. 266 (3): 1620-5; Pourtier-Manzanedo et al. , (1992) Oncol. Res. 4 (11-12); 473-80; Boesch, D. & Loor, F. (1994) Anticancer Drugs 4 (2): 223-9; Zacherl et al. , (1994) Cancer Chemother. Pharmacol. 34 (2): 125-32.; Shirai et al. , (1991); Morris et al. , (1991); Muller et al. , (1994) Int J Cancer. 56 (5): 749-54; and Miyamoto et al. , (1992) Anticancer Res. 12 (3): 649-53. Thalhammer et al. , ((1994) Eur. J. Pharmacol. 270 (2-3): 213-20) showed that the transport mediated by the P-glycoprotein of the cationic acridine orange dye through the bile canaliculi was inhibited by cyclosporin A and the verapamil. The ATP-15-dependent transport of the amphiphilic cations through the hepatocyte canalicular membrane by the p-glycoprotein was also studied by Muller et al. , (1994). He - - Transport of permanently loaded amylic cations was inhibited by verapamil, quinidine and the antibiotic, daunorubicin. Bear (1994) showed that verapamil, colchicine, vinblastine and daunomycin (50 μm) blocked a chloride channel that was rectified outward, and it was proposed that the latter be associated with the expression p-glycoprotein. Ohi et al., (1992) Cancer Chemother. Pharmacol. 30 Suppl: S50-4) used the calcium channel blocker, verapamil with adriamycin in chemotherapy for a superficial bladder cancer. Five ampoules were administered (10 ml) of verapamil injection. The verapamil hydrochloride is benzeneacetonitrile-a- [3- [[2- (3,4-dimethoxy penyl) ethyl] -methylamino] propyl] -3,4-dimethoxy-a- (1-methylethyl) hydrochloride; also called CALAN ™ and ISOPTIN ™, and available with Searle, Knoll and Parke-Davis. Verapamil is absorbed by more than 90%, but only 20 to 35% of the dose reaches the system due to the extensive first step of hepatic metabolism. It binds approximately 90% to plasma proteins. The liver metabolizes it rapidly in nor-verapamil and in indications of numerous other metabolites. Approximately 70% of a dose is excreted in the urine as metabolites, and 16% of a dose appears in the stool over 5 days; less than 5% is excreted without changes. The effects of verapamil are evident throughout 30 to 60 - - minutes from an oral dose. The peak effects of verapamil occur over 15 minutes from its intravenous supply. The half-life is 1.5 to 5 hours in normal people but may exceed 9 hours during a chronic therapy. In subjects with cirrhosis of the liver, the half-life can be increased from 14 to 16 hours. The half-life is increased in subjects with liver disease, due, in part, to an increased volume of distribution. The saturation kinetics have been observed after repeated doses. The preferred dose includes: intravenous, adults, initially 5 to 10 mg (0.075 to 0.15 mg / kg) over a period of 2 min. (3 min in the elderly), followed by 10 mg (0.150 mg / kg) after 30 min. if necessary; children, up to 1 year, initially from 0.1 to 0.2 mg / kg over 2 min. (with ECG monitoring), repeated after 30 min., if necessary; from 1 to 15 years, initially from 0.1 to 0.3 mg / kg, without exceeding 5 mg, repeated after 30 min., if necessary. Oral, adults 80 mg 3 or 4 times per day or 240 mg once a day in sustained release form, gradually increased up to 480 mg per day, if necessary. Verapamil is available in injectable dosage forms of 5 mg / 2mL and 10 mg / 4mL; dosage forms in 40 mg, 80 mg and 120 mg tablets; and sustained release tablets of 240 mg. The preferred amounts of verapamil - - in the compositions and methods of the present invention are in the range of 100-240 mg. This invention also relates to pharmaceutical dosage unit forms for a systemic delivery (oral, topical, transdermal delivery including controlled release of the drug for long-term treatment or prophylaxis), which are useful in the treatment of mammals, including humans. The term "dosage unit form" as used herein and in the claims, refers to physically discrete units suitable as a unit dosage for mammalian subjects, each unit containing a predetermined amount of the essential active ingredients discussed in FIG. present, calculated to produce the desired effect in combination with the required pharmaceutical means that are adapted to said ingredient for routine administration. Dosage unit forms can be prepared according to any method known in the art for the manufacture of pharmaceutical compositions. Remington-The Science and Practice of Pharmacy (21st Edition) (2005), Goodman & Gilman 's The Pharma cologi cal Basis of Therapeutics (11th Edition) (2005) and Ansel' s Pharmaceutical Dosage Forms and Drug Delivery Systems - - Pharmaceutical Dosage Methods and Drug Delivery Systems of Ansel) (8th Edition), edited by Alien et al., Lippincott Williams & Wilkins, (2005). Examples of dosage unit forms according to this invention are tablets, capsules, powders, dragees, and liquid preparations in liquid carriers for oral delivery, elixirs, nebulizers, aerosols, suppositories, and dry or lyophilized preparations for the extemporaneous reconstitution of dry preparations in a liquid vehicle or for nasal administration by inhalation. Preferably, the compositions can be combined and administered simultaneously or in conjunction with a surfactant, carrier, solvent, excipient or diluent. Such additives are known to those skilled in the art and can be found in the Pharmaceutical Excipients Handbook (4th Edition, Rowe, R.C. (editors) Pharmaceutical Press (Chicago, IL, Pharmaceutical Press). As an example, such carriers may include hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose, silicon dioxide and plasticizers such as polyethylene glycol, polyethylene oxide, among others. The solid diluents or carriers for the solid oral pharmaceutical dosage unit forms are selected from the group consisting of lipids, carbohydrates, proteins and mineral solids, for example, starch, - sucrose, lactose, mannitol, kaolin, dicalcium phosphate, polyvinylpyrrolidone, crospovidone, gelatin, acacia, xanthan gum, corn syrup, corn starch, micronized starch, colloidal silicon, talc and the like. The capsules, both hard and soft, are formulated with conventional diluents and excipients, for example, edible oils, talcum, calcium carbonate, calcium stearate, magnesium stearate and the like. Liquid pharmaceutical preparations for oral delivery can be prepared in water or aqueous solutions, such as, for example, sodium carboxymethylcellulose, methylcellulose, acacia, polyvinyl pyrrolidone, crospovidone, polyvinyl alcohol and the like. Such preparations should be stable under the conditions of manufacture and storage, and ordinarily contain in addition to the basic solvent or suspension liquid, condoms of a bactericidal nature and fungicidal agents, for example, parabens, chlorobutanol, benzyl alcohol, phenol, thimerosal, and Similar. In many cases it is preferable to include isotonic agents, for example, sugars such as lactose or mannitol or sodium chloride. Carriers and carriers include vegetable oils, dimethyl sulfoxide (DMSO), water, ethanol, and polyols, for example, glycerol, propylene glycol, liquid polyethylene glycol, polyethylene oxide, and the like.

- The pharmaceutical dosage unit forms are prepared according to the foregoing general description to provide an effective amount of the essential active ingredients by unit dosage form with the adaptation medium for systemic administration. In general, the unit dosage form will contain from 3 to 73% by weight of the essential active ingredients. It will be appreciated that the exact dosage of the essential active ingredient constituting an effective amount for the treatment of a mammal according to the method of the invention, will vary greatly depending on the specific nature of the clinical condition to be treated, the severity of the condition, species of the mammal, age, but and condition of the mammal, mode of delivery of the dosage form and the specific formulation that is being administered. The exact dose required for a given situation can be determined by administering a test dose and observing the clinical response. In general, an effective amount to be administered will be in a range of from about 0.1 mg per kg. to mg per mg per kg of body weight of the recipient, daily. Preferably, they are provided from 0.5 mg / kg to approximately 25 mg / kg daily. In many cases, a single month of supply will affect a noticeable response and will yield the desired result. In cases such as the treatment of immunological conditions, however, it may be desirable to repeat the supplies numerous times daily over periods of time. The compositions of the invention are capable of achieving approximately 50% -90% decrease in immune activation as measured by the number of CD4 / CD69 positive cells divided by the total number of CD4 positive cells (the positive cells are they determine peripheral blood mononuclear cells (PBMCs) by exposure to anti-CD4 and anti-CD69 antibodies, which is explained in more detail in Example 5 below). In another embodiment of the invention, the compositions are capable of achieving approximately 60% -80% decrease in immune activation. In another embodiment of the invention, the compositions are capable of achieving approximately 65% -75% decrease in immune activity. The invention will now be further described by way of the following non-limiting Examples, given by way of illustration of various embodiments of the invention and is not intended to limit the present invention in any way. EXAMPLES Example 1 A mixture of the following ingredients is - - Prepared by mixing manually: An orally given dosage, 1-4, preferably 1-2 times per day is useful in alleviating immunodeficiency in adult humans caused by infectious disease, or other etiological causes. When supplied to a human adult suffering from HIV, from 1 to 4 daily dosage units, the level is adjusted upwards to a normal range. It has been shown that administration of the above dosage unit mixed 1-4 times (preferably 1 or 2 times) per day is useful in alleviating human adult immunodeficiency caused by infectious disease, or other etiological causes. Example 2 The following was prepared: - The effects of the administration of the above are shown after 4 days of delivery on the viral load of peripheral blood lymphocytes infected with a laboratory adapted HIV virus, in Figure 1. As can be seen, MP-1: MIX : y 'MP-1: [fraction (1/2)] MIX exhibited a synergistic therapeutic effect and exceeded the effectiveness of AZT. EXAMPLE 3 The effects of the administration of the above are shown after 4 days of delivery on the viral load of peripheral blood lymphocytes infected by a HAART-resistant clinical viral isolate, in Figure 2. A synergistic therapeutic effect was again demonstrated and a superiority to AZT. Example 4 The effects of verapamil SR 180 and quercetin (150 mg) on the CD4 count and viral load of a hypertensive subject who refused anti-retroviral therapy are shown in Figure 3. It is understood that the proportions and ingredients can be adjusted with the stage of disease as well as with the tolerance of the subject to the individual components. In addition, it is understood that the metabolites of a calcium channel blocker or quinoline in forms can be used - - adequate. It is further understood that the active components of quercetin such as polyphenols, glycosides, flavonoids, and bio-flavonoids can be extracted and used in appropriate proportions to produce the desired results. Example 5 As described above, both HIV and the H5N1 strand of avian influenza are enveloped, single-stranded RNA viruses. There are numerous other parallels between HIV and H5N1. For example, after one entry both HIV and the H5N1 virus promote a strong influx of calcium. In addition, glutathione levels are believed to be predictive of death in both HIV and H5N1 infections, and GSH has protective effects against H5N1 in vi tro. Furthermore, both HIV and H5N1 infections cause a stronger energetic immune response. HIV infects the monoliths and CD4 cells and kills the latter by both direct cytotoxicity and apoptosis that attenuates the immune response. H5N1 infects epithelial cells and causes an uncontrolled pro-inflammatory immune response that induces a so-called "cytosine crisis". This induction of this cytosine crisis is one of the main causes of pathogenicity since it leads to the death of epithelial cells, acute respiratory distress syndrome and, in many cases, death.

- - In view of the above similarities, it was hypothesized that the novel compositions of the present invention could be effective against both HIV and H5N1 infections and that further, the compositions of the present invention could be effective in the treatment or amelioration of other diseases caused. by single-stranded RNA virus, and / or other diseases and medical conditions characterized by the induction of a "cytosine crisis". The experiments were performed on peripheral blood mononuclear cells ("PBMCs") that were treated in vi tro either with glass beads or with the plant lectin phytohemagglutinin ("PHA") which is similar to the hemagglutinin A of the Influenza and were also treated with a composition of the present invention referred to with "PBS119" comprising verapamil 120 mgs, dilantin 200 mgs, chloroquine 100 mgs and quercetin 1200 mg. The treatment of cells with glass beads and / or cross-linked dextrans such as Sephadex G-25 in an inflammatory response that includes an activation of macrophages and the release of pro-inflammatory cytokines from cells. (See Blanckmeister &; Sussdorf, "Macrophage activation by cross-linked dextran" (Activation of macrophages by cross-linking dextran), Journal of Leukocyte Biology, Volume 37 (2), pages 209-219). It is known that the treatment of cells with PHA stimulates the release of cytosine. (See Greaves &Janossy, Transplant, Rev. Volume 11, pages 87 1972). Therefore, treatment of cells with either glass and / or PHA beads provides a useful substitute for the type of immune activation and cytosine crisis induced by H5N1 infection. In addition, because the "cytosine crisis" is believed to be one of the leading causes of death from H5N1 infection, the ability of a drug to reduce the cytosine crisis suggests that the drug will be useful in the treatment of the infection. by H5N1, and also from infection by other agents that cause a cytosine crisis. Approximately 1 million PBMCs were used in Complete medium (consisting of the 1640 Roswell Park Memorial Institute media containing 10% fetal calf serum (FCS), penicillin / streptomycin) for each experimental group. The cells were exposed to either 2 μg of PHA-L or 10 million glass beads. Then the cells in the experimental groups were treated with PBS119. Cells in both control (untreated) and experimental groups were incubated for 96 hours at 37 ° C in a 5% C02 atmosphere. The cells were then harvested, washed three times with saline buffered with physiological phosphate, pelleted by centrifugation and exposed to 100 μg of anti-CD4 and anti-CD69 antibodies (Becton - - Dickinson, Mountainview, CA). The anti-CD4 antibodies were labeled with a green fluorescent label and the anti-CD69 antibodies were labeled with a red fluorescent label. Flow cytometry was then performed using a FACS-Caliber flow cytometer (Becton Dickinson, Mountainview, CA) to detect fluorescent green and red. The number of activated cells was quantified by dividing the number of CD4 / CD69 positive cells by the total number of CD4 positive cells. Cells treated with the compositions of the present invention exhibited a 67 to 75% decrease in immune activation compared to untreated controls. The data suggest that the compositions of the present invention can be used to decrease the immune reactivity associated with H5N1 infection, and to reduce or obliterate the "cytosine crisis" and the resulting development of acute respiratory distress and possibly death in individuals. infected with H5N1. The data also suggest that the compositions of the present invention could be useful in the treatment of other infections and diseases characterized by immune reactivity and the induction of a cytosine crisis. It should be noted that the compositions according to the present invention can vary from the exact amounts and proportions used in this example. By - - example, the compositions can be used and in them the amount of verapamil is in the range of approximately 80-240 mgs, the amount of dilantin is in the range of approximately 100-300 mgs, the amount of chloroquine is in the range of approximately 100-250 mgs and the amount of quercetin is in the range of approximately 1200-2400 mg. Other amounts of these components may also be used. In addition, other calcium channel blockers may be used in place of verapamil, other suitable anti-convulsants may be used in place of dilantin, other suitable quinolines may be used in place of chloroquine, and quercetin derivatives may be used in place of quercetin. It is understood that the exact proportions and ingredients can be adjusted depending on several factors including the disease stage as well as the subject's tolerances towards the individual components. It should also be noted that when treating patients, a multivitamin component should also be used as this will decrease the consequences of the PBS119 components. The multivitamin component has numerous beneficial effects for example it increases the levels of Glutathione, DHEA, selenium, zinc, vitamins C, A and beta carotene. EXAMPLE 6 The therapeutically effective amounts of the compositions of the present invention, including those described in each of the above examples and through the specification of the present invention, are administered to patients infected with avian influenza, including avian influenza strain H5N1. in order to treat the infection. It is understood that the proportions and ingredients can be adjusted depending on the various factors including the stage of disease as well as the tolerances of the subject towards the individual components. Example 7 The compositions described in the U.S. Patent. 6,262,019 raise glutathione (GSH) levels and can be beneficially delivered to patients infected by various viral infections, such as HIV, HCV (hepatitis C) or other viral infections. This is illustrated in Figure 4 which provides a graph illustrating the effects of administration of the compositions described in the U.S. Patent. 6,262,019 on GSH levels in lymphocytes of human patients. It can be seen that the level of GSH is greatly reduced in patients infected with HIV, HCV or other viruses and that treatment with the compositions of the EU Patent: 6,262,019 restores GSH levels to normal or even to higher than normal levels. . It can also be seen that two months after cessation of treatment, - GSH levels decrease to around pre-treatment levels. The compositions of the present invention are beneficially administered in combination with the compositions described in U.S. Patent No. 6,262,019 to patients infected with avian influenza, including avian influenza strain H5N1, in order to treat the infection. It is understood that the proportions and ingredients can be adjusted depending on the various factors including the stage of disease as well as the tolerances of the subject towards the individual components. Example 8 It is believed that the antiviral and other effects of the compositions of the present invention are mediated, at least in part, by the binding of quercetin to CD4 + T cells. This hypothesis was tested in an experiment using strains isolated from PBMCs of patients who had been treated with a composition of the present invention referred to as "PBS119". The composition PBS119 used comprised verapamil 120 mgs, dilantin 200 mgs, chloroquine 100 mgs, and quercetin 1200 mg. Patients also received a multivitamin component that is useful in decreasing the metabolic consequences of PBS119 components. The multivitamin component has numerous beneficial effects for example increasing the - levels of Glutathione, DHEA, selenium, zinc, vitamins C, A and beta carotene. The consistent samples of lxlO6 PMBCs were separated by ficoll-hypaque density gradient separation (Sigma-Aldrich) (specific gravity 1.078). The cells were then suspended in 1 ml of phosphate-buffered saline (PBS), either with or without the addition of 1% Nonidet P40 (Sigma Aldrich). The cells were incubated for 30 minutes in an atmosphere of 5% C02 at 37 degrees humidified. Nonidet P49 is a mild non-ionic detergent, a treatment with which substances not specifically bound from the surface of the cell are removed. The cells were then washed three times in PBS and the cell pellet was suspended in 100 lambda of anti-CD3 / CE4 (Becton Dickinson). The cells were incubated in the presence of the antibodies for 30 minutes at room temperature and then subjected to flow cytometric analysis. The labeling of CD16 / CD45 was used to confine (separate) the lymphocytes. IGG subclass controls (Becton Dickinson) of suitable mice were used. The results of data from a single patient treated with PBS119 are illustrated in Figure 5. It can be seen that a greater number of CD4 + cells were detected in the cell sample that had been treated with 1% Nonidet P40. It is believed that this is because the PBS119, in particular the - Quercetin component of PBS119, has been "washed" by the NP-40 thus allowing the anti-CD4 antibody to bind to the cells. Vice versa, it can be seen that a smaller number of CD4 + cells was detected in the cell sample that was not treated with 1% NP40, the reason is because PBS119, in particular the quercetin component of PBS119, does not specifically bind to the cells thus preventing the anti-CD4 antibody from binding. As a control, Figure 5 also shows the data from a single patient treated with HAART and illustrates that there is no significant difference in the binding of the anti-CD4 to these cells that have been treated with Nonidet P40, presumably because there was not a substance not specifically linked to these cells that blocked the binding with the anti-CD4. The graph represented in Figure 5 represents one among a number of comparative experiments. It was not possible to combine data from multiple patients due to large variations in the initial CD4 cell counts. It is believed that the antiviral activity of the compositions of the present invention comprising quercetin against other viruses, such as the avian influenza virus can be mediated, at least in part, by a binding of quercetin to the surface of other cell types in addition. of the T cells. For example, it is believed that the compositions of the present invention comprising quercetin also bind to cells such as epithelial cells. It is also believed that the compositions of the present invention comprising quercetin may bind to the surface of other cell types. For example, it is believed that the compositions of the present invention comprising quercetin may bind to / block the hepatocytes and thereby block or inhibit the binding of the Hepatitis C virus. It should be noted that the compositions according to the present invention can vary from the exact amounts used to treat patients in this example. For example, the compositions can be used and in them the amount of verapamil is in the range of approximately 80-240 mgs, the amount of dilantin is in the range of approximately 100-300 mgs, the amount of chloroquine is found in the range of approximately 100-250 mgs, the amount of quercetin is in the range of approximately 1200-2400 mg. Other amounts of these components may also be used. In addition, other suitable calcium channel blockers may be used in place of verapamil, other suitable anti-convulsants may be used in place of dilantin, other suitable quinolines may be used in place of chloroquine, and quercetin derivatives may be used in place of quercetin. It is understood that the exact proportions and ingredients can be adjusted depending on several factors including the disease stage as well as the subject's tolerances towards the individual components. Having thus described in detail the preferred embodiments of the present invention, it should be understood that the invention defined by the appended claims should not be limited by the particular details set forth in the foregoing description since many apparent variations thereof are possible without departing from the spirit or scope of it.

Claims (48)

1. - CLAIMS 1. An antiviral composition comprising at least one component of the calcium channel blocker, an anti-convulsant component, a quinoline component or derivatives thereof, and a multivitamin component in amounts sufficient to treat and reduce viral activity in an infected subject.
2. 2. The composition of claim 1, further comprising a quercetin component or derivatives thereof.
3. The composition of claim 1, wherein the weight ratio of the calcium channel blocker component to the quinoline component relative to the anti-seizure component is from about 100-240 mg to about 200-250 mg up to approximately 100-300 mg.
4. The composition of claim 1, wherein the anti-convulsant component comprises phenytoin or derivatives thereof.
5. The composition of claim 1, wherein the quinoline component comprises at least one member selected from the group consisting of chloroquine, mefloquine, mefloquine hydrochloride, primaquine, primaquine phosphate, carboxyprimaquine, and derivatives thereof.
6. 6. The composition of claim 1, in - wherein the calcium channel blocker component comprises at least one member selected from the group consisting of verapamil, nimodipine, diproteverin, drug No. 9512 of SmithKine, isoptine, nitrendipine, diltiazam, myoflazine, flunarizine, bepridil, lidoflazine, CERM-196 , R-58735, R-56865, ranolazine, nisoldipine, nicardipine, PNZ00-110, felodipine, amlodipine, R- (+) - 202-791, R - (+) Bay K-8644, and derivatives thereof.
7. The composition of claim 1, wherein the multivitamin component comprises β-carotene, N-acetylcysteine, glucosamine, Vitamin C, Vitamin D, Vitamin E, calcium, magnesium, boron, zinc, and chromium piconolate.
8. The composition of claim 1, wherein the components are in particle and tablet form with pharmaceutically acceptable tablet-forming agents or carriers.
9. The composition of claim 1, wherein the components are in combination with a pharmaceutically acceptable liquid carrier.
10. The composition of claim 1 comprising about 100-240 mg of the calcium channel blocker component and about 200-250 mg of the quinoline component.
11. A method for reducing viral activity in an infected subject, comprising administering to the subject a therapeutically effective amount of a composition comprising at least one component of the calcium channel blocker, an anticonvulsant component, a component of quinoline or derivatives thereof, and a multivitamin component, in sufficient amounts to treat and reduce viral activity in a subject.
12. The method of claim 11, further comprising a quercetin component or derivatives thereof.
13. The method of claim 11, wherein the weight ratio of the calcium channel blocker component to the quinoline component and the anti-seizure component is from about 100 mg to about 200 mg to about 300 mg.
14. The method of claim 11, wherein the anti-convulsant component comprises phenytoin or derivatives thereof.
15. The method of claim 11, wherein the quinoline component comprises at least one member selected from the group consisting of chloroquine, mefloquine, mefloquine hydrochloride, primaquine, primaquine phosphate, carboxyprimaquine, and derivatives thereof.
16. The method of claim 11, wherein the calcium channel blocker component comprises at least one member selected from the group consisting of verapamil, nimodipine, diproteverin, drug No. 9512 of SmithKine, isoptine, nitrendipine, diltiazam, myoflazine, flunarizine, bepridil, lidoflazine, CERM-196, R-58735, R-56865, ranolazine, nisoldipine, nicardipine, PNZ00-110, felodipine, amlodipine, R- (+) - 202-791, R - (+) Bay K-8644, and derivatives thereof.
17. The method of claim 11, wherein the multivitamin component comprises β-carotene, N-acetylcysteine, glucosamine, Vitamin C, Vitamin D, Vitamin E, calcium, magnesium, boron, zinc, and chromium piconolate.
18. 18. The method of claim 11, wherein the components are in the form of a particle and a tablet with pharmaceutically acceptable tablet-forming agents or carriers.
19. The method of claim 11, wherein the components are in combination with a pharmaceutically acceptable liquid carrier.
20. The method of claim 11 comprising about 100-240 mg of the calcium channel blocker component and about 200-250 mg of the quinoline component.
21. 21. A method for reducing viral activity in an infected subject, comprising administering to the subject a therapeutically effective amount of the composition of claim 1.
22. 22. A method for increasing glutathione levels in a virally infected subject, which comprises administering to the subject a therapeutically effective amount of a composition comprising at least one component of the calcium channel blocker, an anti-convulsant component, a quinoline component or derivatives thereof, and a multivitamin component, in amounts enough to increase glutathione levels in the subject.
23. 23. The method of claim 22 further comprising a quercetin component or derivatives thereof.
24. The method of claim 22 wherein the weight ratio of the calcium channel blocker component to the quinoline component and the anti-seizure component is from about 100 mg to about 200 mg to about 300 mg.
25. 25. The method of claim 22 wherein the anti-convulsant component comprises phenytoin or derivatives thereof.
26. 26. The method of claim 22 wherein the quinoline component comprises at least one member selected from the group consisting of chloroquine, mefloquine, mefloquine hydrochloride, primaquine, phosphate - of primaquine, carboxyprimaquine and derivatives thereof.
27. The method of claim 22 wherein the calcium channel blocker component comprises at least one member selected from the group consisting of verapamil, nimodipine, diproteverin, drug No. 9512 of SmithKine, isoptine, nitrendipine, diltiazam, myoflazine, flunarizine, bepridil, lidoflazine, CERM-196, R-58735, R-56865, ranolazine, nisoldipine, nicardipine, PNZ00-110, felodipine, amlodipine, R- (+) -202-791, R - (+) Bay K- 8644, and derivatives thereof.
28. The method of claim 22 wherein the multivitamin component comprises β-carotene, N-acetylcysteine, glucosamine, Vitamin C, Vitamin D, Vitamin E, calcium, magnesium, boron, zinc, and chromium piconolate.
29. 29. The method of claim 22 wherein the components are in particle and tablet form with pharmaceutically acceptable tablet-forming agents or carriers.
30. 30. The method of claim 22 wherein the components are in combination with a pharmaceutically acceptable liquid carrier.
31. 31. The method of claim 22 comprising about 100 to 240 mg of the calcium channel blocker component and about 200 to 250 mg of the quinoline component. -
32. 32. A method for increasing glutathione levels in a virally infected subject, comprising administering to the subject a therapeutically effective amount of the composition of claim 1.
33. 33. A method for reducing the activity of a single-stranded RNA virus in a cell infected by the virus or a subject infected by the virus, comprising administering to the cell or subject a therapeutically effective amount of a composition comprising: (i) quercetin or derivatives thereof; (ii) at least one component of the calcium channel blocker; (iii) an anti-convulsive component; (iv) a quinoline component or derivatives thereof; and (v) a multivitamin component, in sufficient amounts to treat and reduce viral activity in the cell or subject.
34. 34. The method according to claim 33, wherein the single-stranded RNA virus is selected from the group comprising HIV and an avian influenza virus.
35. 35. The method according to claim 34, wherein the avian influenza virus is an H5N1 avian influenza virus.
36. 36. A method to reduce a pro- inflammatory and / or cytosine crisis in a cell or in a subject, comprising administering to the cell or subject a therapeutically effective amount of a composition comprising: (i) quercetin or derivatives thereof; (ii) at least one component of the calcium channel blocker; (iii) an anti-convulsive component; (iv) a quinoline component or derivatives thereof; and (v) a multivitamin component, in amounts sufficient to treat and reduce the pro-inflammatory response and / or cytosine crisis in the cell or subject.
37. 37. The method according to claim 36 wherein the pro-inflammatory response and / or cytosine crisis are the result of an infection of the cell or subject with a pathogenic agent.
38. 38. The method according to claim 37 wherein the pathogen is a virus.
39. 39. The method according to claim 38 wherein the virus is an avian influenza virus.
40. 40. The method according to claim 39 wherein the avian influenza virus is the avian influenza virus H5N1.
41. 41. The method of claim 33 wherein: the amount of quercetin or a derivative thereof is from about 1200-2440 mg; the amount of at least one component of the calcium channel blotter is from about 80-240 mg; the amount of an anti-convulsant component is from about 100-300 mg; and the amount of the quinoline component or derivative thereof is from about 100-250 mg;
42. 42. The method according to claim 33 wherein: the quercetin or derivative thereof is quercetin; the at least one component of the calcium channel blocker is verapamil; the quinoline component or derivative thereof is chloroquinine; and the anti-convulsant component is dilantin.
43. 43. The method according to claim 41 wherein: the quercetin or derivative thereof is quercetin; the at least one component of the calcium channel blocker is verapamil; the quinoline component or derivative thereof is chloroquinine; and - the anti-convulsant component is dilantin.
44. 44. The method according to claim 33 wherein the decrease in immune activation is from about 50% to about 90%.
45. 45. The method of claim 36 wherein: the amount of quercetin or derivative thereof is from about 1200-2440 mg; the amount of at least one component of the calcium channel blocker is from about 80-240 mg; the amount of an anti-convulsant component is from about 100-300 mg; and the amount of the quinoline component or derivative thereof is from about 100-250 mg.
46. 46. The method according to claim 36 wherein: the quercetin or derivative thereof is quercetin; the at least one component of the calcium channel blocker is verapamil; the quinoline component or derivative thereof is chloroquinine; and the anti-convulsant component is dilantin.
47. 47. The method according to claim 46 wherein: the quercetin or derivative thereof is quercetin; - - the at least one component of the calcium channel blocker is verapamil; the quinoline component or derivative thereof is chloroquinine; and the anti-convulsant component is dilantin.
48. 48. The method of claim 36 wherein the decrease in immune activation is from about 50% to about 90%.