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Basic Characteristics of Mutations
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Mutation Site
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S31N |
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Mutation Site Sentence
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Virtual Screening Identifies Chebulagic Acid as an Inhibitor of the M2(S31N) Viral Ion Channel and Influenza A Virus. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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M2 |
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Standardized Encoding Gene
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M
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Genotype/Subtype
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- |
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Viral Reference
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A/Puerto Rico/8/34 (PR8)
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Functional Impact and Mechanisms
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Disease
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Influenza A
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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Adamantane |
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Location
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- |
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Literature Information
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PMID
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32599753
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Title
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Virtual Screening Identifies Chebulagic Acid as an Inhibitor of the M2(S31N) Viral Ion Channel and Influenza A Virus
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Author
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Duncan MC,Onguene PA,Kihara I,Nebangwa DN,Naidu ME,Williams DE,Balgi AD,Andrae-Marobela K,Roberge M,Andersen RJ,Niikura M,Ntie-Kang F,Tietjen I
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Journal
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Molecules (Basel, Switzerland)
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Journal Info
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2020 Jun 24;25(12):2903
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Abstract
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The increasing prevalence of drug-resistant influenza viruses emphasizes the need for new antiviral countermeasures. The M2 protein of influenza A is a proton-gated, proton-selective ion channel, which is essential for influenza replication and an established antiviral target. However, all currently circulating influenza A virus strains are now resistant to licensed M2-targeting adamantane drugs, primarily due to the widespread prevalence of an M2 variant encoding a serine to asparagine 31 mutation (S31N). To identify new chemical leads that may target M2(S31N), we performed a virtual screen of molecules from two natural product libraries and identified chebulagic acid as a candidate M2(S31N) inhibitor and influenza antiviral. Chebulagic acid selectively restores growth of M2(S31N)-expressing yeast. Molecular modeling also suggests that chebulagic acid hydrolysis fragments preferentially interact with the highly-conserved histidine residue within the pore of M2(S31N) but not adamantane-sensitive M2(S31). In contrast, chebulagic acid inhibits in vitro influenza A replication regardless of M2 sequence, suggesting that it also acts on other influenza targets. Taken together, results implicate chebulagic acid and/or its hydrolysis fragments as new chemical leads for M2(S31N) and influenza-directed antiviral development.
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Sequence Data
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-
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