Certain purine nucleosides have proved to be effective antivirals and are used as systemic agents. Two of these antiviral drugs deserve special mention. Vidarabine, or araA, is used topically for ocular herpesvirus and systemically for herpetic encephalitis as well as for neonatal herpesviral infections. This drug is an adenosine derivative that is phosphorylated by cellular enzymes to a triphosphate compound that inhibits many viral and human DNA polymerases and thus DNA synthesis. Herpesviral enzymes are ∼20-fold more susceptible to the drug compared with host DNA. Vidarabine is administered IV in large volumes of fluid and is rapidly inactivated. It may produce bone marrow suppression and CNS side effects when high blood levels are reached. An ophthalmic solution also is available.
Acyclovir (acycloguanosine) represents a new generation of antiviral agents, mainly because of its unique mechanism of action. This purine nucleoside is phosphorylated more efficiently by virus-induced thymidine kinase compared with host thymidine kinase. Once activated to the triphosphate form, it is a better substrate and inhibitor of viral, compared with host, DNA polymerase. Binding to DNA polymerase is irreversible. Once incorporated into viral DNA, the DNA chain is terminated.
Acyclovir is relatively safe (probenecid renders the drug safer) and is useful against a variety of infections caused by DNA viruses, especially the herpesvirus family. However, resistance is increasing. Acyclovir is unable to eliminate latent infections. It is available as an ophthalmic ointment, a topical ointment and cream, an IV preparation, and various oral formulations. The prodrug deoxyacyclovir is more readily absorbed from the GI tract than acyclovir. Another similar antiviral purine nucleoside analog is ganciclovir, a synthetic guanine that is effective against human cytomegalovirus. Its mechanism of action is similar to that of acyclovir.
Last full review/revision March 2012 by Dawn Merton Boothe, DVM, PhD, DACVIM, DACVCP