A patient with suspected herpes simplex infection is treated with acyclovir. This drug inhibits which viral enzyme?

• A. RNA polymerase
• B. DNA polymerase
• C. Helicase
• D. Topoisomerase

Answer: (B)

Acyclovir works by mimicking a building block of DNA and becoming activated mainly in infected cells. After entering a herpes-infected cell, the drug is phosphorylated first by viral thymidine kinase to become acyclovir monophosphate, then by cellular kinases to the active triphosphate form. This active form is preferentially used by the viral DNA polymerase, where it competes with the natural deoxyguanosine triphosphate. Once incorporated, it lacks a 3’ hydroxyl group, so DNA synthesis cannot continue—leading to chain termination. The result is inhibition of viral DNA replication rather than transcription or other viral processes.

Because acyclovir relies on viral thymidine kinase for activation, it selectively targets viral DNA polymerase in infected cells, sparing most of the host’s enzymes. It does not inhibit RNA polymerase, nor does it directly inhibit helicase or topoisomerase; those enzymes are involved in other aspects of replication or unwinding but are not the primary targets of acyclovir.