Acyclovir (acycloguanosine) and its l-valyl ester prodrug valacyclovir, represent a new generation of antiviral agents, mainly because of the unique mechanism of action. This purine nucleoside is phosphorylated more efficiently by virus-induced thymidine kinase than host thymidine kinase. Once activated to the triphosphate form, it is a better substrate and inhibitor of viral, versus host, DNA polymerase. Binding to DNA polymerase is irreversible. Once acyclovir is 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 analogue is ganciclovir, a synthetic guanine effective against human cytomegalovirus. Its mechanism of action is similar to that of acyclovir.