Abstract
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.
MeSH terms
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Amino Acid Sequence
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Antiviral Agents / pharmacology*
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Carbamates
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Cell Line
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Drug Resistance, Viral
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Genes, Reporter
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Genotype
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Hepacivirus / drug effects*
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Hepacivirus / physiology
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Humans
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Imidazoles / pharmacology*
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Inhibitory Concentration 50
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Luciferases / genetics
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Molecular Sequence Data
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Pyrrolidines
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Replicon / genetics
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Valine / analogs & derivatives
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Viral Nonstructural Proteins / antagonists & inhibitors*
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Viral Nonstructural Proteins / genetics
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Viral Nonstructural Proteins / metabolism
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Virus Replication / drug effects
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Virus Replication / genetics
Substances
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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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Luciferases
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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/JQ347513
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GENBANK/JQ347514
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GENBANK/JQ347515