Resistance outside the substrate envelope: hepatitis C NS3/4A protease inhibitors.

ABSTRACT: Direct acting antivirals have dramatically increased the efficacy and tolerability of hepatitis C treatment, but drug resistance has emerged with some of these inhibitors, including nonstructural protein 3/4 A protease inhibitors (PIs). Although many co-crystal structures of PIs with the NS3/4A protease have been reported, a systematic review of these crystal structures in the context of the rapidly emerging drug resistance especially for early PIs has not been performed. To provide a framework for designing better inhibitors with higher barriers to resistance, we performed a quantitative structural analysis using co-crystal structures and models of HCV NS3/4A protease in complex with natural substrates and inhibitors. By comparing substrate structural motifs and active site interactions w

SUBMITTER: Ozen A 

PROVIDER: S-EPMC7717897 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature