Antiherpesvirus, anti-hepatitis virus, and anti-respiratory virus agents

This chapter reviews agents which have been, or are being, developed to treat herpesvirus, hepatitis virus, and respiratory virus infections. Detailed information is provided for approved agents and those in more advanced stages of clinical development. Agents in phase I human studies or promising approaches which are still in preclinical development are described briefly. The anti-herpes simplex virus (HSV) activity of acyclovir demonstrated that analogs of guanosine were active and that acyclic side chains could substitute for the ribose moiety, conferring specificity by the selective uptake and activation of acyclovir in HSV-infected cells. Thymidine kinase-deficient or -altered HSV or varicella-zoster virus (VZV) isolates resistant to acyclovir remain susceptible in vitro to foscarnet, cidofovir, and brivudine but are fully cross-resistant to ganciclovir and famciclovir. The more convenient dosing schedule of famciclovir and the potentially shorter duration of postherpetic neuralgia argue in favor of employing famciclovir or valacyclovir for herpes zoster, particularly in older individuals, in whom the complication of postherpetic neuralgia is more frequent. Cidofovir has been primarily developed as an anti-CMV agent but has broad antiherpesvirus activity. New antiherpesvirus drugs include inhibitors of immediate early gene expression, nonnucleoside DNA polymerase inhibitors, helicase-primase inhibitors, inhibitors of protein-protein interactions among DNA replication proteins, and inhibitors of assembly, encapsidation, and nuclear egress. The chapter describes agents that are primarily or exclusively directed at treatment of hepatitis virus infection. Antiviral activities of ribavirin are also described.