Recent advances in the analysis of HCV NS5B RNA-dependent RNA polymerase

An RNA-dependent RNA polymerase denoted nonstructural protein 5B (NS5B) is the central enzyme in replication of the hepatitis C virus genome. Recent advances in the biochemical and structural understanding of NS5B include solubilization and purification of the full-length enzyme and various truncated forms. In vitro conditions for NS5B-catalyzed primer elongation using both homo- and heteropolymeric RNA templates were discovered. The crystal structure of the NS5B apoenzyme revealed a globular shape unique among polymerases, and implicated new structural features important for binding the RNA template and cognate ribonucleotide substrates. The crystallographic results also provided a structure-based framework for biochemical analyses and drug-design efforts. Finally, inhibitors of HCV RNA-dependent RNA polymerase have been reported.