Acyclovir selectively inhibits viral DNA synthesis in herpesvirus-infected cells while sparing host cells. The principal basis for this selectivity is:
- A Host cells lack nucleoside transporters required for drug entry
- B Acyclovir binds only viral RNA polymerase and has no activity against human polymerases
- C Initial phosphorylation depends on a viral thymidine kinase with much higher affinity for acyclovir than cellular thymidine kinase ✓
- D Herpesviruses actively pump the drug into infected cells through a virally encoded transporter
Correct answer: C. Initial phosphorylation depends on a viral thymidine kinase with much higher affinity for acyclovir than cellular thymidine kinase
Explanation
Acyclovir is a guanosine analogue that must be converted to the triphosphate to inhibit viral DNA polymerase. The first phosphorylation step is performed almost exclusively by herpesvirus thymidine kinase, which has far greater affinity for acyclovir than the host enzyme, so the activated drug accumulates mainly in infected cells. Viral DNA polymerase inhibition then terminates chain elongation. Host cells are spared largely because they phosphorylate acyclovir poorly, not because of transport differences.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.