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
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Amino Acid Sequence
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Amino Acid Substitution / drug effects
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Amino Acid Substitution / genetics*
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Amino Acids / genetics
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Antiviral Agents / pharmacology*
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Carbamates
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Genotype
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Hepacivirus / drug effects
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Hepacivirus / genetics*
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Imidazoles / pharmacology*
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Molecular Sequence Data
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Pyrrolidines
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Reassortant Viruses / drug effects
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Reassortant Viruses / genetics*
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Replicon / drug effects
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Valine / analogs & derivatives
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Viral Nonstructural Proteins / genetics*
Substances
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Amino Acids
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Antiviral Agents
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Carbamates
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Imidazoles
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Pyrrolidines
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Viral Nonstructural Proteins
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NS-5 protein, hepatitis C virus
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Valine
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daclatasvir
Associated data
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GENBANK/JX944789
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GENBANK/JX944790
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GENBANK/JX944791