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Structural basis for RNA replication by the hepatitis C virus polymerase

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Science  13 Feb 2015:
Vol. 347, Issue 6223, pp. 771-775
DOI: 10.1126/science.1259210

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A view of the HCV polymerase at work

More than 3% of the world's population is infected with hepatitis C virus (HCV), a predisposing factor for life-threatening liver diseases such as cirrhosis and cancer. HCV encodes a polymerase called NS5B that catalyzes replication of the viral RNA genome. Drugs inhibiting NS5B have shown impressive antiviral activity in recent clinical trials. Appleby et al. (see the Perspective by Bressanelli) reveal the inner workings of HCV RNA replication by analyzing crystal structures of stalled NS5B polymerase ternary complexes during the initiation and elongation of RNA synthesis. They also define the way in which sofosbuvir, a drug with potent clinical efficacy, interacts with the NS5B active site.

Science, this issue p. 771; see also p. 715