title: In vitro activity of daclatasvir on hepatitis C virus genotype 3 NS5A.
abstract: The NS5A replication complex inhibitor daclatasvir (DCV; BMS-790052) inhibits hybrid replicons containing hepatitis C virus (HCV) genotype 3a (HCV3a) NS5A genes with 50% effective concentrations (EC(50)s) ranging from 120 to 870 pM. Selection studies with a hybrid HCV3a replicon identified NS5A residues 31 and 93 as sites for DCV-selected resistance. Our results support the potential use of DCV as a component in combination therapies for HCV3a chronic infection.
authors.affiliation: Department of Virology, Bristol-Myers Squibb Research and Development, Wallingford, Connecticut, USA.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Wang
authors.forename: Lourdes
authors.initials: L
authors.lastname: Valera
authors.forename: Lingling
authors.initials: L
authors.lastname: Jia
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Kirk
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Robert A
authors.initials: RA
authors.lastname: Fridell
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000187:drug effects / Q000235:genetics*; D000596:Amino Acids / Q000235:genetics; D000998:Antiviral Agents / Q000494:pharmacology*; D002219:Carbamates; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D007093:Imidazoles / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011759:Pyrrolidines; D016865:Reassortant Viruses / Q000187:drug effects / Q000235:genetics*; D012093:Replicon / Q000187:drug effects; D014633:Valine / Q000031:analogs & derivatives; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000596:Amino Acids; D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D014633:Valine; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C549273:daclatasvir