title: Characterization of V36C, a novel amino acid substitution conferring hepatitis C virus (HCV) resistance to telaprevir, a potent peptidomimetic inhibitor of HCV protease.
abstract: 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.
authors.affiliation: Department of Virology, Hôpital Henri Mondor, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Barbotte
authors.forename: Abdelhakim
authors.initials: A
authors.lastname: Ahmed-Belkacem
authors.forename: Stéphane
authors.initials: S
authors.lastname: Chevaliez
authors.forename: Alexandre
authors.initials: A
authors.lastname: Soulier
authors.forename: Christophe
authors.initials: C
authors.lastname: Hézode
authors.forename: Henri
authors.initials: H
authors.lastname: Wajcman
authors.forename: Doug J
authors.initials: DJ
authors.lastname: Bartels
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Andrzej
authors.initials: A
authors.lastname: Ardzinski
authors.forename: Nagraj
authors.initials: N
authors.lastname: Mani
authors.forename: B Govinda
authors.initials: BG
authors.lastname: Rao
authors.forename: Shelley
authors.initials: S
authors.lastname: George
authors.forename: Ann
authors.initials: A
authors.lastname: Kwong
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
mesh_terms: D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics; D014644:Genetic Variation; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C486464:telaprevir