Abstract
The identification of a novel hit compound inhibitor of the protein-protein interaction between the influenza RNA-polymerase PA and PB1 subunits has been accomplished by means of high-throughput screening. A small family of structurally related molecules has been synthesized and biologically evaluated with most of the compounds showing micromolar potency of inhibition against viral replication.
Keywords:
Antiviral agents; Benzofurazan; H1N1; Influenza virus; Viral RNA polymerase.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiviral Agents / chemical synthesis
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Antiviral Agents / chemistry
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Antiviral Agents / toxicity*
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Benzoxazoles / chemical synthesis
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Benzoxazoles / chemistry*
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Benzoxazoles / toxicity
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DNA-Directed RNA Polymerases / chemistry
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DNA-Directed RNA Polymerases / metabolism*
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Dogs
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Drug Evaluation, Preclinical
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / toxicity
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Influenza A virus / drug effects*
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Influenza A virus / enzymology
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Madin Darby Canine Kidney Cells
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Protein Interaction Domains and Motifs / drug effects
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Protein Subunits / chemistry
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Protein Subunits / metabolism
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Structure-Activity Relationship
Substances
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Antiviral Agents
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Benzoxazoles
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Enzyme Inhibitors
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Protein Subunits
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benzofurazan
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DNA-Directed RNA Polymerases