Viral DNA polymerase inhibitor
- A nucleoside analogue phosphorylated by the VIRAL kinase (thymidine kinase, UL97) — uninfected cells barely activate it
- The triphosphate is incorporated and terminates the chain → ↓ herpesvirus replication
- Ganciclovir also inhibits human DNA polymerase → myelosuppression; acyclovir does not
- Chain termination of viral DNA synthesis
- Aciclovir requires viral thymidine kinase, giving selectivity
- Nephrotoxicity with rapid IV infusion
Drugs with this mechanism (5)
- Acyclovir — Guanosine-analog antiviral for herpes; activated by viral thymidine kinase.
- Adefovir — Superseded HBV nucleotide; nephrotoxic with a low resistance barrier.
- Cidofovir — Antiviral for CMV; nephrotoxic, given with probenecid.
- Ganciclovir — IV antiviral for severe CMV disease; marrow suppression is the major limit.
- Penciclovir — Topical antiviral for cold sores and the active drug released from famciclovir; modest benefit with frequent application.
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