Antiviral mechanisms

The antiviral mechanism of action of acyclovir has been reviewed (72). Acyclovir is converted to the monophosphate in herpes vims-infected cells (but only to a limited extent in uninfected cells) by viral-induced thymidine kinase. It is then further phosphorylated by host cell guanosine monophosphate (GMP) kinase to acyclovir diphosphate [66341 -17-1], which in turn is phosphorylated to the triphosphate by unidentified cellular en2ymes. Acyclovir triphosphate [66341 -18-2] inhibits HSV-1 viral DNA polymerase but not cellular DNA polymerase. As a result, acyclovir is 300 to 3000 times more toxic to herpes vimses in an HSV-infected cell than to the cell itself. Studies have shown that a once-daily dose of acyclovir is effective in prevention of recurrent HSV-2 genital herpes (1). HCMV, on the other hand, is relatively uninhibited by acyclovir. 

Abstract In 2007, the world celebrated the 50th anniversary of the discovery of interferon (IFN) by Isaacs and Lindemnann. Subsequently, the IFN-a gene was cloned, fully sequenced and IFN-a was produced in recombinant form. Recombinant IFN-a is now used as the basis for treatment of chronic hepatitis C virus infection and can also be used to treat certain forms of chronic hepatitis B virus infections. IFNs have also been used in other viral infections, although with less success. The antiviral mechanisms of IFNs are reviewed in this chapter as well as the utility of IFNs in the treatment of persistent viral infections. 

Antiviral mechanisms (A). The organism can disrupt viral replication with the aid of cytotoxic T-lymphocytes that recognize and destroy virus-producing cells (viral surface proteins) or Ltillmann, Color Atlas of Pharmacology... 

Pharmacology A fluorinated pyrimidine nucleoside with in vitro and in vivo activity against herpes simplex virus types 1 and 2, and vaccinia virus. Some strains of adenovirus are also inhibited in vitro. Its antiviral mechanism of action is not completely known. 

Bellenamine, (R)-3,6-diamino-V-(aminomethyl)hexanamide is a (very) small-molecular-weight (MW 174) antibiotic produced by Streptomyces nashvillensis. It has only weak antibacterial activity but inhibits HIV-1 infection at an IC50 of 0.62 pg/ml (3.6 iM). With a CC50 of > 2 mg/ml (11.5 mM), the selectivity index of bellenamine can be estimated at well above 2000. Similarl to the well-established glycosylation inhibitors castanospermine and 1-deoxynojirimycin, bellenamine inhibits the secondary spread of HIV, although, unlike the glycosylation inhibitors, bellenamine had no apparent inhibitory effect on the glycosylation process. Therefore, its antiviral mechanism remains to be elucidated. 

Mode of action The precise antiviral mechanism of amantadine... 

Mode of action The precise antiviral mechanism of amantadine and rimantadine remains to be established. Recent evidence points to a blockade of the viral membrane matrix protein, M2, which functions as an ion channel. This channel is required for the fusion of the viral membrane with the cell membrane that ultimately forms the endosome (created when the virus is internalized by endocytosis). [Note The acid environment of the endosome is required for viral uncoating.] These drugs may also interfere with the release of new virions. 

Like idoxuridine. the antiviral mechanism of trifluridinc involves inhibition of viral DNA synthesis. Trifluridinc monophosphate is an irreversible inhibitor of thymidylate synthetase, and the biologically generated triphosphate competitively inhibits thymidine triphosphate incorporation into DNA by DNA polymera.se. In addition, trilluridine in its triphosphate form is incorporated into viral and cellular DNA. creating fragile, poorly functioning DNA. 

Koszalka GW, Meanwell NA (2006) Inhibition of virus entry an antiviral mechanism of emerging prominence. Curr Opin Investig Drugs 7 106-108... 

The antiviral mechanism of action of ribavirin relates to alteration of cellular nucleotide pools and inhibition of viral messenger RNA synthesis. Intracellular phosphorylation to the mono-, di-, and triphosphate derivatives is mediated by host cell enzymes. In both uninfected and RSV-infected cells, the predominant derivative (>80%) is the triphosphate, which has an intracellular t,/2 of elimination of less than 2 hours. 

The antiviral mechanism of action of triflnridine involves inhibition of viral DNA synthesis. Triflnridine monophosphate irreversibly inhibits thymidylate synthetase, and trifluridine triphosphate is a competitive inhibitor of thymidine triphosphate incorporation into DNA by DNA polymerases. Trifluridine is incorporated into viral and ceUnlar DNA. Trifluridine-resistant HSV with altered thymidine kinase substrate specificity can be selected in vitro, and resistance in clinical isolates has been described. 

Although the precise antiviral mechanism of ribavirin is not known, the... 

B Antiviral mechanism of action related with various nanoparticles ... 

Volume 20 - Antiviral Mechanisms in the Control of Neoplasia edited by P. Chandra... 

From the green leafy part of Welsh onion (Allium fistulosum L.) a fructan was isolated displaying an in-vivo anti-influenza A virus activity after oral administration in mice. Despite the observed in-vivo effect, the fructan did not exhibit in-vitro efficacy in MDK cells infected with influenza A virus. The antiviral mechanism could be dependent on the host immime system [96]. 

Several studies, some of them mentioned above, have suggested that some of the antiviral mechanisms of AMPs are due to their action on host cells, rather than in parallel with their direct action to inactivate viral particles. For example, they may make fish cells more resistant to and/or protected from viral infections. Cecropins are a family of linear AMPs initially discovered in giant silk moth (//. with no members found in... 

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