Naturally occurring NS3-protease-inhibitor resistant mutant A156T in the liver of an untreated chronic hepatitis C patient.
An increasing number of new hepatitis C virus NS3-protease inhibitors are being evaluated for the treatment of chronic hepatitis C. Treatment-induced selection of mutants conferring resistance to protease inhibitors has been shown both in vivo and in vitro. A specific mutation, A156T has been shown to confer high-level resistance to several such agents (BILN2061, VX-950, SCH446211 (SCH6) and SCH503034). Here we report the presence of the A156T mutation in close to 1% of NS3 sequences within the liver quasispecies of a chronic hepatitis C patient never treated with anti-NS3-protease inhibitors.
Cubero
Maria
M
Liver Unit, Department of Medicine, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Esteban
Juan Ignacio
JI
Otero
Teresa
T
Sauleda
Silvia
S
Bes
Marta
M
Esteban
Rafael
R
Guardia
Jaume
J
Quer
Josep
J
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002219:Carbamates / Q000494:pharmacology; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D005814:Genes, Viral; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D008099:Liver / Q000821:virology; D047028:Macrocyclic Compounds / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D017354:Point Mutation; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D012697:Serine Endopeptidases / Q000235:genetics*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D002219:Carbamates; D004279:DNA, Viral; D047028:Macrocyclic Compounds; D009842:Oligopeptides; D011392:Proline; D011804:Quinolines; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors; D013844:Thiazoles; D017361:Viral Nonstructural Proteins; C479555:BILN 2061; C084422:NS3 protein, hepatitis C virus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C510133:SCH6; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide