Clinical Context: Acyclovir is a prodrug activated through phosphorylation by a virus-specific thymidine kinase that inhibits viral replication. Herpesvirus thymidine kinase (TK), but not host-cell TK, converts acyclovir into acyclovir monophosphate, a nucleotide analogue. Guanylate kinase converts the monophosphate into diphosphate and triphosphate analogues that inhibit viral DNA replication. Once phosphorylated, the drug causes DNA chain termination when acted on by DNA polymerase. It interferes with DNA replication within the virions.