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.
Barbotte
Laetitia
L
Department of Virology, Hôpital Henri Mondor, France.
Ahmed-Belkacem
Abdelhakim
A
Chevaliez
Stéphane
S
Soulier
Alexandre
A
Hézode
Christophe
C
Wajcman
Henri
H
Bartels
Doug J
DJ
Zhou
Yi
Y
Ardzinski
Andrzej
A
Mani
Nagraj
N
Rao
B Govinda
BG
George
Shelley
S
Kwong
Ann
A
Pawlotsky
Jean-Michel
JM
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
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