In vitro resistance profile of the hepatitis C virus NS3/4A protease inhibitor TMC435.

  title={In vitro resistance profile of the hepatitis C virus NS3/4A protease inhibitor TMC435.},
  author={Oliver Lenz and Thierry Verbinnen and Tse-I Lin and Leen Vijgen and Maxwell D Cummings and Jimmy Lindberg and Jan Martin Berke and Pascale Dehertogh and Els Fransen and Annick Scholliers and Katrien Vermeiren and Tania Ivens and Pierre Raboisson and Michael Edlund and Susan Storm and Lotta Vrang and Herman A de Kock and Gregory C Fanning and Kenneth A Simmen},
  journal={Antimicrobial agents and chemotherapy},
  volume={54 5},
TMC435 is a small-molecule inhibitor of the NS3/4A serine protease of hepatitis C virus (HCV) currently in phase 2 development. The in vitro resistance profile of TMC435 was characterized by selection experiments with HCV genotype 1 replicon cells and the genotype 2a JFH-1 system. In 80% (86/109) of the sequences from genotype 1 replicon cells analyzed, a mutation at NS3 residue D168 was observed, with changes to V or A being the most frequent. Mutations at NS3 positions 43, 80, 155, and 156… CONTINUE READING
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