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The Hepatitis C virus (HCV) NS5B protein is a nonstructural protein that functions as an RNA-dependent RNA polymerase (RdRp). It is essential for the replication of the HCV genome, catalyzing the synthesis of new viral RNA strands using the positive-sense viral RNA as a template. NS5B catalyzes the polymerization of ribonucleoside triphosphates (rNTPs) during viral genome replication. This process involves de novo initiation, meaning it can start synthesizing new RNA without a primer, which is crucial for efficient viral propagation. The enzyme binds to both structured and unstructured regions of the viral RNA template in different modes and undergoes conformational changes upon nucleotide binding to facilitate catalysis. NS5B is a prime target for antiviral drugs against HCV.
Nucleotide analogues: Mimic natural substrates; cause premature chain termination. Non-nucleotide inhibitors: Bind allosteric sites on NS5B, impairing function without being incorporated into growing RNAs.
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