Novel non-nucleoside inhibitors of the HCV RNA polymerase (NS5b) with sub-micromolar biochemicalpotency have been identified which are selective for the inhibition of HCV NS5b over other polymerases.The structures of the complexes formed between several of these inhibitors and HCV NS5b were determinedby X-ray crystallography, and the inhibitors were found to bind in an allosteric binding site separate fromthe active site. Structure-activity relationships and structural studies have identified the mechanism of actionfor compounds in this series, several of which possess drug-like properties, as unique, reversible, covalentinhibitors of HCV NS5b.
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