In vitro activity of daclatasvir on hepatitis C virus genotype 3 NS5A

Antimicrob Agents Chemother. 2013 Jan;57(1):611-3. doi: 10.1128/AAC.01874-12. Epub 2012 Oct 22.

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.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution / drug effects
  • Amino Acid Substitution / genetics*
  • Amino Acids / genetics
  • Antiviral Agents / pharmacology*
  • Carbamates
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics*
  • Imidazoles / pharmacology*
  • Molecular Sequence Data
  • Pyrrolidines
  • Reassortant Viruses / drug effects
  • Reassortant Viruses / genetics*
  • Replicon / drug effects
  • Valine / analogs & derivatives
  • Viral Nonstructural Proteins / genetics*

Substances

  • Amino Acids
  • Antiviral Agents
  • Carbamates
  • Imidazoles
  • Pyrrolidines
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus
  • Valine
  • daclatasvir

Associated data

  • GENBANK/JX944789
  • GENBANK/JX944790
  • GENBANK/JX944791