Characterization Of V36c, A Novel Amino Acid Substitution Conferring Hepatitis C Virus (Hcv) Resistance To Telaprevir, A Potent Peptidomimetic Inhibitor Of Hcv Protease

We characterized a novel substitution conferring moderate resistance to telaprevir, a peptidomimetic inhibitor of hepatitis C virus protease. V36C conferred a 4.0-fold increase in the telaprevir 50% inhibitory concentration in an enzyme assay and a 9.5-fold increase in the replicon model. The replication capacity of a replicon harboring V36C was close to that of the wild-type protease. This case emphasizes the complexity of hepatitis C virus resistance to protease inhibitors.