Abstract
A novel class of non-nucleoside HCV NS5B polymerase inhibitors has been identified from screening. A co-crystal structure revealed an allosteric binding site in the protein that required a unique conformational change to accommodate inhibitor binding. Herein we report the structure-activity relationships (SARs) of this novel class of dihydropyrone-containing compounds that show potent inhibitory activities against the HCV RNA polymerase in biochemical assays.
MeSH terms
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Crystallography, X-Ray
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DNA-Directed RNA Polymerases / antagonists & inhibitors*
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DNA-Directed RNA Polymerases / chemistry
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DNA-Directed RNA Polymerases / metabolism
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Hepacivirus / drug effects*
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Hepacivirus / enzymology*
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Hydrogen / chemistry*
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Inhibitory Concentration 50
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Models, Molecular
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Molecular Structure
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Pyrones / chemical synthesis
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Pyrones / chemistry*
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Pyrones / pharmacology*
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RNA-Dependent RNA Polymerase / antagonists & inhibitors
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RNA-Dependent RNA Polymerase / chemistry
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Structure-Activity Relationship
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Viral Nonstructural Proteins / chemistry
Substances
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Pyrones
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Viral Nonstructural Proteins
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Hydrogen
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NS-5 protein, hepatitis C virus
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RNA-Dependent RNA Polymerase
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DNA-Directed RNA Polymerases