How is acyclovir activated in the body?

Acyclovir is a nucleoside analog that exhibits its antiviral properties primarily through its conversion to its active form by viral thymidine kinase. This enzyme is produced by certain herpes viruses, including HSV (Herpes Simplex Virus) and VZV (Varicella-Zoster Virus).

When acyclovir enters infected cells, it is phosphorylated by viral thymidine kinase to form acyclovir monophosphate. Further phosphorylation occurs with the help of human cellular kinases, resulting in the formation of acyclovir triphosphate, which is the active metabolite. This active form inhibits viral DNA polymerase, thereby terminating viral DNA synthesis and replication, which leads to the antiviral effects observed in the treatment of infections caused by these viruses.

The activation of acyclovir is significant because it selectively affects virus-infected cells due to the dependency on the viral thymidine kinase for its initial phosphorylation step, resulting in a more targeted action compared to other antiviral medications. This selective activation contributes to the low toxicity of acyclovir to uninfected cells.