In vitro resistance profile of the hepatitis C virus NS3 protease inhibitor BI 201335.
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.
Boehringer Ingelheim (Canada) Ltd., Laval, Québec, Canada H7S2G5.
Lisette
L
Lagacé
Peter W
PW
White
Christiane
C
Bousquet
Nathalie
N
Dansereau
Florence
F
Dô
Montse
M
Llinas-Brunet
Martin
M
Marquis
Marie-Josée
MJ
Massariol
Roger
R
Maurice
Catherine
C
Spickler
Diane
D
Thibeault
Ibtissem
I
Triki
Songping
S
Zhao
George
G
Kukolj
D019943:Amino Acid Substitution; D000621:Aminoisobutyric Acids; D000998:Antiviral Agents / Q000494:pharmacology; D018360:Crystallography, X-Ray; D024882:Drug Resistance, Viral; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology; D006801:Humans; D020128:Inhibitory Concentration 50; D016898:Interferon-alpha / Q000494:pharmacology*; D007700:Kinetics; D007930:Leucine / Q000031:analogs & derivatives; D016297:Mutagenesis, Site-Directed; D059645:Mutation Rate; D009842:Oligopeptides / Q000494:pharmacology*; D010641:Phenotype; D011392:Proline / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000494:pharmacology; D011804:Quinolines; D012093:Replicon; D013844:Thiazoles / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000621:Aminoisobutyric Acids; D000998:Antiviral Agents; D016898:Interferon-alpha; D007930:Leucine; D009842:Oligopeptides; D011392:Proline; D011480:Protease Inhibitors; D011804:Quinolines; D013844:Thiazoles; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C552340:faldaprevir