In vitro resistance profile of the hepatitis C virus NS3 protease inhibitor BI 201335

Antimicrob Agents Chemother. 2012 Jan;56(1):569-72. doi: 10.1128/AAC.05166-11. Epub 2011 Oct 24.

Abstract

The in vitro resistance profile of BI 201335 was evaluated through selection and characterization of variants in genotype 1a (GT 1a) and genotype 1b (GT 1b) replicons. NS3 R155K and D168V were the most frequently observed resistant variants. Phenotypic characterization of the mutants revealed shifts in sensitivity specific to BI 201335 that did not alter susceptibility to alpha interferon. In contrast to macrocyclic and covalent protease inhibitors, changes at V36, T54, F43, and Q80 did not confer resistance to BI 201335.

MeSH terms

  • Amino Acid Substitution
  • Aminoisobutyric Acids
  • Antiviral Agents / pharmacology
  • Crystallography, X-Ray
  • Drug Resistance, Viral
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / enzymology
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / virology
  • Humans
  • Inhibitory Concentration 50
  • Interferon-alpha / pharmacology*
  • Kinetics
  • Leucine / analogs & derivatives
  • Mutagenesis, Site-Directed
  • Mutation Rate
  • Oligopeptides / pharmacology*
  • Phenotype
  • Proline / analogs & derivatives
  • Protease Inhibitors / pharmacology
  • Quinolines
  • Replicon
  • Thiazoles / pharmacology*
  • Viral Nonstructural Proteins / genetics*
  • Viral Nonstructural Proteins / metabolism

Substances

  • Aminoisobutyric Acids
  • Antiviral Agents
  • Interferon-alpha
  • NS3 protein, hepatitis C virus
  • Oligopeptides
  • Protease Inhibitors
  • Quinolines
  • Thiazoles
  • Viral Nonstructural Proteins
  • faldaprevir
  • Proline
  • Leucine