Acyclovir is used for herpes simplex encephalitis. It is selectively phosphorylated in HSV-infected cells. Which viral enzyme accomplishes the first, rate-limiting phosphorylation step?

• A Viral thymidine kinase (TK) ✓
• B Viral DNA polymerase
• C Viral helicase-primase complex
• D Host cell adenylate kinase

Explanation

Acyclovir is a nucleoside analogue prodrug (guanosine analogue). The first and rate-limiting phosphorylation to acyclovir monophosphate is performed by the virus-encoded thymidine kinase (TK), which is expressed only in HSV-infected cells—ensuring selective activation. Host cell kinases then convert the monophosphate to acyclovir triphosphate, which is incorporated by viral DNA polymerase as a chain terminator (lacking a 3'-OH group). This selective activation explains both efficacy and low host cell toxicity. Resistance arises most commonly from TK mutations.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.