In vitro activity of BMS-790052 on hepatitis C virus genotype 4 NS5A.
The antiviral profile of BMS-790052, a potent hepatitis C virus (HCV) replication complex inhibitor targeting nonstructural protein NS5A, is well characterized for HCV genotype-1. Here, we report that BMS-790052 inhibits hybrid replicons containing HCV genotype-4 NS5A genes with 50% effective concentrations (EC(50)s) ranging from 7 to 13 pM. NS5A residue 30 was an important site for BMS-790052-selected resistance in the hybrid replicons. Our results support the potential of BMS-790052 as a valuable component of combination therapy for HCV genotype-4 chronic infection.
Department of Virology, Bristol-Myers Squibb Research and Development, Wallingford, Connecticut, USA.
Chunfu
C
Wang
Lingling
L
Jia
Haichang
H
Huang
Dike
D
Qiu
Lourdes
L
Valera
Xin
X
Huang
Jin-Hua
JH
Sun
Peter T
PT
Nower
Donald R
DR
O'Boyle
Min
M
Gao
Robert A
RA
Fridell
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology*; D002219:Carbamates; D002460:Cell Line; D024882:Drug Resistance, Viral; D017930:Genes, Reporter; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008156:Luciferases / Q000235:genetics; D008969:Molecular Sequence Data; D011759:Pyrrolidines; D012093:Replicon / Q000235:genetics; D014633:Valine / Q000031:analogs & derivatives; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D008156:Luciferases; D011759:Pyrrolidines; D014633:Valine; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C549273:daclatasvir