Alternative antiviral agents

Alternative antiviral agents for the treatment of drug-resistant herpesviruses are the acyclic nucleoside phosphonate analogs. The lead compound of this new series of antiviral molecules is cidofovir [(S)-l-(3-hydroxy-2-phosphonylmethoxypropyljcytosine] (HPMPC), which has a broad-spectrum antiviral activity in vitro and in vivo against several DNA viruses. Cidofovir has been approved for the treatment of CMV retinitis in AIDS patients, and it has also been shown to be effective in the treatment of persistent mucocutaneous infections caused by ACVr HSV and ACVr/PFAr HSV (6,7). 

Acyclovir-resistant HSV has been isolated from patients with AIDS. The primary mechanism of resistance appears to be a deficiency in viral thymidine kinase. Strategies that have been employed for management of severe acyclovir-resistant HSV infections include increasing the dose of acyclovir, discontinuing acyclovir, and use of an alternative antiviral agent. Vidarabine and foscarnet, because they do not require phosphorylation by thymidine kinase, are examples of potential alternative agents. A randomized comparison of foscarnet and vidarabine indicated that foscarnet is more effective and associated with fewer adverse reactions than vidarabine. ... 

Many drugs, including antibiotics and antiviral agents, operate by inhibiting critical enzyme-catalyzed reactions or serve as alternative dead-end substrates of such reactions. 

In cultured primary duck hepatocytes (PDH) congenitally infected with duck hepatitis B virus (DHBV), all major viral replicative intermediates are generated, and CCC DNA, present initially at a low copy number, is amplified in the PDH after a few days in culture (4,5), The amplification of CCC DNA in vitro provides an alternative to liver analysis for studying the structure of this molecule and its sensitivity to potential antiviral agents. 

Andrei, G., Snoeck, R., and De Clercq, E. (1995) Susceptibilities of several drug-resistant herpes simplex virus type 1 strains to alternative antiviral compounds. Antimicrob. Agents Chemother. 39,1632-1635. 

Santoyo, S., Plaza, M., Jaime, L., Ibaftez, E., Reglero, G., Senorans, F.J., 2010. Pressurized liquid extraction as an alternative process to obtain antiviral agents from the edible microalga CMorella vulgaris. Journal of Agricultural and... 

It was concluded previously (11) that FMAU is a most potent and selective antiviral compound for the treatment of mouse encephalitis caused by HSV-2 and therefore deserved consideration as a potential agent in human trials for the treatment of HSV encephalitis in neonates and adults at low dose levels. The preliminary data described in Tables I and II for FEAU suggested (10) that this compound may also be worthy of similar consideration. Based upon these earlier findings (10) and on our preliminary biochemical report (12). further comparative biochemical and antiviral studies were undertaken with FMAU and FEAU, including their relative activities against Simian varicella vims in the African green monkey and against hepatitis vims in the woodchuck animal model. In these studies (13) an alternative synthesis of FEAU is also described. 

Piscitelli SC, Amantea MA, Vogel S, Bechtel C, Metcalf JA, Kovacs JA. Effects of cjdokines on antiviral pharmacokinetics an alternative approachtoassessmentof drug interactions using bioequivalence guidelines, Antimicrob Agents Chemother (1996) 40,161-5. 

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