A 24-year-old patient with genital herpes is prescribed acyclovir. The drug's selectivity for infected cells over normal cells is primarily due to:

• A Higher cellular uptake of acyclovir by virus-infected cells
• B Acyclovir being a prodrug activated by host cell cytochrome P450
• C Selective expression of the acyclovir transporter only on herpes-infected cells
• D Preferential phosphorylation of acyclovir by viral thymidine kinase in infected cells ✓

Explanation

Acyclovir is a nucleoside analogue that must be phosphorylated to its active triphosphate form to inhibit viral DNA polymerase. The first and rate-limiting phosphorylation is catalyzed by viral thymidine kinase (TK), which is expressed only in herpes-infected cells. Host cell kinases are poor substitutes for this first step. Thus the drug accumulates preferentially as acyclovir triphosphate in infected cells, giving a selective index several hundred-fold higher in virus-infected cells compared to uninfected cells.

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

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Written and medically reviewed by the StethoPrep medical team.