Naturally occurring NS3-protease-inhibitor resistant mutant A156T in the liver of an untreated chronic hepatitis C patient

Virology. 2008 Jan 20;370(2):237-45. doi: 10.1016/j.virol.2007.10.006. Epub 2007 Nov 19.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Carbamates / pharmacology
  • DNA, Viral / genetics
  • Drug Resistance, Viral / genetics
  • Genes, Viral
  • Hepacivirus / drug effects
  • Hepacivirus / enzymology*
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / virology*
  • Humans
  • Liver / virology
  • Macrocyclic Compounds / pharmacology
  • Male
  • Molecular Sequence Data
  • Oligopeptides / pharmacology
  • Point Mutation*
  • Proline / analogs & derivatives
  • Proline / pharmacology
  • Quinolines / pharmacology
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Serine Endopeptidases / genetics*
  • Serine Proteinase Inhibitors / pharmacology
  • Thiazoles / pharmacology
  • Viral Nonstructural Proteins / genetics*

Substances

  • BILN 2061
  • Carbamates
  • DNA, Viral
  • Macrocyclic Compounds
  • NS3 protein, hepatitis C virus
  • Oligopeptides
  • Quinolines
  • SCH6
  • Serine Proteinase Inhibitors
  • Thiazoles
  • Viral Nonstructural Proteins
  • telaprevir
  • 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
  • Proline
  • Serine Endopeptidases

Associated data

  • GENBANK/EF613694
  • GENBANK/EF613695
  • GENBANK/EF613696
  • GENBANK/EF613697
  • GENBANK/EF613698
  • GENBANK/EF613699
  • GENBANK/EF613700
  • GENBANK/EF613701
  • GENBANK/EF613702
  • GENBANK/EF613703
  • GENBANK/EF613704
  • GENBANK/EF613705
  • GENBANK/EF613706
  • GENBANK/EF613707
  • GENBANK/EF613708
  • GENBANK/EF613709
  • GENBANK/EF613710
  • GENBANK/EF613711
  • GENBANK/EF613712
  • GENBANK/EF613713
  • GENBANK/EF613714
  • GENBANK/EF613715
  • GENBANK/EF613716
  • GENBANK/EF613717
  • GENBANK/EF613718
  • GENBANK/EF613719
  • GENBANK/EF613720
  • GENBANK/EF613721
  • GENBANK/EF613722
  • GENBANK/EF613723
  • GENBANK/EF613724
  • GENBANK/EF613725