CHARACTERIZATION OF V36C, A NOVEL AMINO ACID SUBSTITUTION CONFERRING HEPATITIS C VIRUS (HCV) RESISTANCE TO TELAPREVIR, A POTENT PEPTIDOMIMETIC INHIBITOR OF HCV PROTEASE

2 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 telaprevir inhibitory concentration 50 % 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. 3 Advances in virology have led to the development of novel therapeutics specifically targeting hepatitis C virus (HCV) (4). Telaprevir (VX-950, Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts) is a novel, highly selective potent peptidomimetic inhibitor of HCV nonstructural protein 3/4A (NS3/4A) protease (1, 3), which has reached Phase III clinical development in combination with pegylated IFN-α and ribavirin. Amino acids substitutions conferring telaprevi