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Basic Characteristics of Mutations
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Mutation Site
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N31S |
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Mutation Site Sentence
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The anti-influenza virus activity of compounds 2, 3, 7 and 19, that inhibited the V27A channel (Table 1), was also determined in MDCK cells using a 46-h virus PRA with the A/WSN/33 virus (H1N1 subtype), which carries a N31S/V27A M2 protein. |
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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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H1N1 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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-
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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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- |
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Location
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HongKong |
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Literature Information
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PMID
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28418242
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Title
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Slow but Steady Wins the Race: Dissimilarities among New Dual Inhibitors of the Wild-Type and the V27A Mutant M2 Channels of Influenza A Virus
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Author
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Barniol-Xicota M,Gazzarrini S,Torres E,Hu Y,Wang J,Naesens L,Moroni A,Vazquez S
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Journal
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Journal of medicinal chemistry
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Journal Info
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2017 May 11;60(9):3727-3738
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Abstract
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New insights on the amantadine resistance mechanism of the V27A mutant were obtained through the study of novel, easily accessible 4-(1- and 2-adamantyl)piperidines, identified as dual binders of the wild-type and V27A mutant M2 channels of influenza A virus. Their antiviral activity and channel blocking ability were determined using cell-based assays and two-electrode voltage clamp (TEVC) technique on M2 channels, respectively. In addition, electrophysiology experiments revealed two interesting findings: (i) these inhibitors display a different behavior against the wild-type versus V27A mutant A/M2 channels, and (ii) the compounds display antiviral activity when they have k(d) equal or smaller than 10(-6) while they do not exhibit antiviral activity when k(d) is 10(-5) or higher although they may show blocking activity in the TEV assay. Thus, caution must be taken when predicting antiviral activity based on percent channel blockage in electrophysiological assays. These findings provide experimental evidence of the resistance mechanism of the V27A mutation to wild-type inhibitors, previously predicted in silico, offer an explanation for the lack of antiviral activity of compounds active in the TEV assay, and may help design new and more effective drugs.
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Sequence Data
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-
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