Mode of antiviral activity

Amino-5-iodo-2, 5 -dideoxyuridine [56045-73-9] (13) C2H22IN2O4, was synthesized ia 1975 (27) and was found effective against herpes keratitis ia rabbits (28). This compound is markedly less cytotoxic than IdU, iadicating that it may have a safer and more specific mode of antiviral activity. A potential limitation of this group of nucleosides is their specificity, for they fail to inhibit all strains of herpes vimses. The specific antiviral activity of (13) is considered to be a result of the incorporation of the 5 -Ai-phosphate into both viral and host DNA in infected cells, but not into the DNA of normal cells. Phosphorylation of (13) occurs only in herpes vims-infected cells, brought about by a vims-induced thymidine kinase (29). 

Other natural sources of anti-HSV PS include fungi, e g., various protein bound PS isolated from Ganoderma lucidum, a basidiomycetous fungus used to treat human diseases in oriental folk medicine [98], The possible mode of antiviral activity of these PS seems to be related to their binding with HSV-specific glycoproteins responsible for attachment and... 

Eo SK, Kim YS, Lee CK et al (2000) Possible mode of antiviral activity of acidic protein bound polysaccharide isolated from Ganoderma lucidum on herpes simplex viruses. J Ethnopharmacol 72 475-481... 

Thia-8-oxoguanosine 5-amino-3-p-D-ribofuranosylthiazolo[4,5- pyrimidine-2,7(3fJ,6.Ff)-dione, 59 [122970 40-5] synthesized by ICN Pharmaceuticals, (138) has shown broad-spectmm antiviral activity. 7-Thia-8-oxoguanosine, C10H12N4O6S, is highly active in mice and rats against Semliki Forest, San Angelo, benzi, rat corona, and encephalomyocarditis viruses when administered intraperitoneaUy before exposure to the vims (139). The compound was moderately effective in mice infected intraperitoneaUy with HSV-2 or intranasaUy with vesicular stomatitis vims. The mode of antiviral action of (59) in vivo may be due in part to the induction of interferon Ot (138). 

Carbocyclic 2, 3 -didehydro-2, 3 -dideoxyguanosine [118353-05-2] (carbovir, CBV, 66), C H N O synthesized in 1988 (177),is apromising candidate for the chemotherapy of AIDS. CBV inhibits HIV replication and HIV-induced cytopathic effects in a variety of human T-lymphoblastoid cell lines at concentrations approximately two hundred- to four hundredfold below its cytotoxic concentrations (177). CBV is as effective as AZT and DDC in reducing the expression of viral antigen in HIV-infected CEM cells (177). The antiviral potency and selectivity of carbovir is comparable to the anti-HIV-1 potency and selectivity of 2, 3 -dideoxyadenosine (178). The exact mode of antiviral action of carbovir has not yet been elucidated, but may be the modulating effect of intracellular nucleotides on 5 -nucleotidase activity (179). 

The antiviral activity of (5)-DHPA in vivo was assessed in mice inoculated intranasaHy with vesicular stomatitis vims ( 5)-DHPA significantly increased survival from the infection. (5)-DHPA did not significantly reduce DNA, RNA, or protein synthesis and is not a substrate for adenosine deaminase of either bacterial or mammalian origin. However, (5)-DHPA strongly inhibits deamination of adenosine and ara-A by adenosine deaminase. Its mode of action may be inhibition of Vadenosyl-L-homocysteine hydrolase (61). Inhibition of SAH hydrolase results in the accumulation of SAH, which is a product inhibitor of Vadenosylmethionine-dependent methylation reactions. Such methylations are required for the maturation of vital mRNA, and hence inhibitors of SAH hydrolase may be expected to block vims repHcation by interference with viral mRNA methylation. 

A crucial issue for antiviral therapy is the fact that all antiviral substances rapidly select for resistance thus, monitoring and overcoming resistance has become a most important clinical paradigm of antiviral therapy. This calls for cautious use of antiviral drugs and implementation of combination therapies. In parallel, efforts in drug discovery have to be continued to develop compounds with novel mode-of-action and activity against resistant strains. This book reviews the current status of antiviral therapy, from the roads to development of new compounds to their clinical use and cost effectiveness. Individual chapters address in more detail all available drug classes and outline new approaches currently under development. 

Pharmacology Inhibits the replication of influenza A virus isolates from each of the subtypes. Amantadine s antiviral activity is not completely understood. Its mode of action appears to be the prevention of the release of infectious viral nucleic acid P.1044... 

Ninomiya Y, Shimma N, Ishitsuka H. Comparative studies on the antirhino virus activity and mode of action of the rhinovirus capsid binding agents, chalcone amides. Antivir Res 1990 13 61-74. 

Mode of action AZT must be converted to the corresponding nucleoside triphosphate by mammalian thymidine kinase in order for it to exert its antiviral activity. AZT-triphosphate is then incorporated into the growing chain of viral (but not mammalian nuclear) DNA by reverse transcriptase1. Because AZT lacks a hydroxyl at the 3 position, another 5 -3 phosphodiester linkage cannot be formed. Thus, synthesis of the DNA chain is terminated, and replication of the virus cannot take place. The relative lack of discrimination of the viral reverse transcriptase is believed to favor the introduction of the AZT into the viral-catalyzed process the cellular DNA polymerase is more selective. In addition, the phosphory-... 

M. J. Carlucci, M. Ciancia, M. C. Matulewicz, A. S. Cerezo, and E. B. Damonte, Antiherpetic activity and mode of action of natural carrageenans of diverse structural types, Antiviral Res., 43 (1999) 93-102. 

Amantadine The antiviral efficacy of amantadine was first reported by w. Davies et al. in 1964. The mode of action consists in preventing uncoating and viral maturation (inhibition of the release of the nucleic acids that have already penetrated the host cell). The active substance is almost completely absorbed following oral intake. It is eliminated unchanged via the kidneys. Half-life is about 16 hours. So far, it has been used to combat influenza virus type A. Tolerance is good. Amantadine on its own is only minimally effective against HCV it is therefore not suitable for initial monotherapy. 

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