Acyclovir is highly selective for HSV/VZV-infected cells over uninfected cells. The basis for this selectivity is:

• A Acyclovir is only absorbed by cells expressing the herpes-specific cell surface receptor gC
• B Cellular enzymes convert acyclovir to its active form, but the viral DNA polymerase has 1000-fold greater affinity for the triphosphate
• C Infected cells upregulate nucleoside transporters that import acyclovir faster than uninfected cells
• D Acyclovir is converted to acyclovir monophosphate ONLY by virus-encoded thymidine kinase (TK), concentrating the active form in infected cells ✓

Explanation

Acyclovir is a prodrug requiring three phosphorylation steps to become the active acyclovir triphosphate. The critical first step — phosphorylation to acyclovir monophosphate — is catalyzed almost exclusively by the virus-encoded thymidine kinase (TK) of HSV/VZV. Human cell TK phosphorylates acyclovir with >10,000-fold lower efficiency. Once monophosphorylated (in infected cells), cellular kinases complete the phosphorylation. The triphosphate then inhibits viral DNA polymerase competitively and causes chain termination after incorporation.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.