Comparison of the [formula omitted] genotoxicity of penciclovir (PCV) acyclovir (ACV), ganciclovir (GCV), and caffeine (CAF) : J. de G. Mitchell, P. Haynes and T. R. Lambert. SmithKline Beecham Pharmaceuticals, Welwyn, Herts AL6 9AR, UK

Abstract

The chapter discusses the developments in the anti-viral field, with the exclusion of HIV. The virus-specific anti-herpes agents, such as acyclovir, ganciclovir, and foscarnet have had a significant impact on the management of herpesvirus infections. Concomitant, with the use of these agents, has been an increase in the emergence of drug-resistant virus strains. Acyclovir continues to be the major treatment of choice for herpes simplex infections, including cold sores and genital herpes. Famciclovir & the diacetyl, 6-deoxy oral prodrug of penciclovir have been licensed for herpes zoster. Phosphonate isosteres of nucleotides continue to receive attention as agents active against a wide range of herpes viruses. The isonucleosides are another class of nucleosides, with a different sugar template surrogate. Carbocyclic nucleosides continue to be exploited as novel, metabolically stable antiherpes compounds. Mappicine ketone is an analogue of camptothecin and inhibits a broad range of herpesviruses, including herpes simplex virus (HSV)-1, HSV-2, and cytomegalovirus (CMV), with a potency comparable to that of ACV. It is inactive against other DNA and RNA viruses, is not an inhibitor of the mammalian topoisomrase-1, and inhibits a different viral target than ACV or camptothecin. The need for new classes of anti-HSV compounds, with novel mechanisms of viral inhibition, is becoming increasingly acute as mutants resistant to conventional nucleoside and pyrophosphate analogues emerge, especially in the vulnerable immunocompromised patients.