Abstract
We characterized a novel substitution conferring moderate resistance to telaprevir, a peptidomimetic inhibitor of hepatitis C virus protease. V36C conferred a 4.0-fold increase in the telaprevir 50% inhibitory concentration in an enzyme assay and a 9.5-fold increase in the replicon model. The replication capacity of a replicon harboring V36C was close to that of the wild-type protease. This case emphasizes the complexity of hepatitis C virus resistance to protease inhibitors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Substitution
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology*
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Drug Resistance, Viral / genetics
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Genetic Variation
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Hepacivirus / drug effects*
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Hepacivirus / enzymology
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Hepacivirus / genetics*
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Hepatitis C / drug therapy
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Hepatitis C / virology
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Humans
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In Vitro Techniques
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Models, Molecular
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Molecular Mimicry
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Oligopeptides / chemistry
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Oligopeptides / pharmacology*
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Serine Proteinase Inhibitors / chemistry
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Serine Proteinase Inhibitors / pharmacology*
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Viral Nonstructural Proteins / antagonists & inhibitors
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Viral Nonstructural Proteins / chemistry
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Viral Nonstructural Proteins / genetics
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Virus Replication / drug effects
Substances
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Antiviral Agents
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NS3 protein, hepatitis C virus
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Oligopeptides
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Serine Proteinase Inhibitors
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Viral Nonstructural Proteins
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telaprevir