A patient with relapsed/refractory hepatitis C genotype 1 is prescribed sofosbuvir/ledipasvir. Sofosbuvir's mechanism of action and the specific step it targets in HCV replication is:
- A Sofosbuvir inhibits HCV NS5A protein preventing viral assembly and release
- B Sofosbuvir is a covalent inhibitor of HCV NS3/4A serine protease blocking polyprotein cleavage
- C Sofosbuvir is a uridine nucleotide prodrug that, after intracellular phosphorylation to active triphosphate, acts as a chain-terminating nucleotide analogue inhibitor of HCV NS5B RNA-dependent RNA polymerase (RdRp) ✓
- D Sofosbuvir blocks clathrin-mediated HCV endocytosis into hepatocytes by inhibiting scavenger receptor B1 (SR-B1)
Explanation
Sofosbuvir is a uridine nucleotide prodrug (phosphoramidate prodrug technology) that is hydrolyzed intracellularly to the active triphosphate form. This active metabolite competitively inhibits HCV NS5B RNA-dependent RNA polymerase (RdRp) and acts as a chain terminator because its 2'-fluoro, 2'-methyl modification lacks the 3'-OH necessary for further nucleotide addition, halting HCV RNA synthesis. NS5B is pan-genotypic and essential for HCV replication. Ledipasvir targets NS5A (viral replication complex protein). NS3/4A protease inhibitors are drugs ending in '-previr' (e.g., glecaprevir).
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.