Sofosbuvir, a cornerstone of interferon-free therapy for chronic hepatitis C, achieves sustained virological response by directly inhibiting which viral target?

• A NS3/4A serine protease required for polyprotein processing
• B NS5A phosphoprotein essential for replication complex assembly
• C E2 envelope glycoprotein binding to CD81
• D NS5B RNA-dependent RNA polymerase ✓

Explanation

Sofosbuvir is a uridine nucleotide prodrug whose active metabolite terminates HCV RNA synthesis by inhibiting the NS5B RNA-dependent RNA polymerase, the enzyme that replicates the viral genome. Ledipasvir and daclatasvir inhibit NS5A, and simeprevir or paritaprevir inhibit the NS3/4A protease. E2-CD81 interaction is an entry step targeted by no approved drug. Combining agents against two non-overlapping targets prevents resistance emergence.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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