Abstract
Allosteric inhibition of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase enzyme has recently emerged as a viable strategy toward blocking replication of viral RNA in cell-based systems. We report here a novel class of allosteric inhibitor of NS5B that shows potent affinity for the NS5B enzyme and effective inhibition of subgenomic HCV RNA replication in HUH-7 cells. Inhibitors from this class have promising characteristics for further development as anti-HCV agents.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetamides / chemical synthesis*
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Acetamides / pharmacokinetics
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Acetamides / pharmacology
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Administration, Oral
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Allosteric Regulation
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Animals
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Biological Availability
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Cell Line, Tumor
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Hepacivirus / drug effects*
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Hepacivirus / genetics
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Humans
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / pharmacology
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RNA, Viral / biosynthesis
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RNA, Viral / drug effects
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RNA-Dependent RNA Polymerase / antagonists & inhibitors*
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Rats
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Structure-Activity Relationship
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Viral Nonstructural Proteins / antagonists & inhibitors*
Substances
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Acetamides
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Indoles
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RNA, Viral
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Viral Nonstructural Proteins
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NS-5 protein, hepatitis C virus
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RNA-Dependent RNA Polymerase