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Quinolones as HCV NS5B polymerase inhibitors
Dange V Kumar1, Roopa Rai, Ken A Brameld
1Myriad Pharmaceuticals, 305 Chipeta Way, Salt Lake City, UT 84108, USA.
Abstract:
Hepatitis C virus (HCV) infection is treated with a combination of peginterferon alfa-2a/b and ribavirin. To address the limitations of this therapy, numerous small molecule agents are in development, which act by directly affecting key steps in the viral life-cycle. Herein we describe our discovery of quinolone derivatives, novel small-molecules that inhibit NS5b polymerase, a key enzyme of the viral life-cycle. A crystal structure of a quinoline analog bound to NS5B reveals that this class of compounds binds to allosteric site-II (non-nucleoside inhibitor-site 2, NNI-2) of this protein.
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