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Basic Characteristics of Mutations
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Mutation Site
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Q54H |
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Mutation Site Sentence
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Q54H is one of the residues involved in the hydrogen bond network of the model by Barakat and colleagues and indeed the substitution for histidine (H) provides an additional hydrogen bond that was lost upon the mutation R30Q, and the histidine may assume the same positive charge as the arginine. |
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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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NS5A |
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Standardized Encoding Gene
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NS5A
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Genotype/Subtype
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1b |
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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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HCV Infection
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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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- |
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Literature Information
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PMID
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29986475
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Title
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Epistatic Interactions in NS5A of Hepatitis C Virus Suggest Drug Resistance Mechanisms
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Author
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Knops E,Sierra S,Kalaghatgi P,Heger E,Kaiser R,Kalinina OV
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Journal
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Genes
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Journal Info
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2018 Jul 6;9(7):343
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Abstract
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Hepatitis C virus (HCV) causes a major health burden and can be effectively treated by direct-acting antivirals (DAAs). The non-structural protein 5A (NS5A), which plays a role in the viral genome replication, is one of the DAAs’ targets. Resistance-associated viruses (RAVs) harbouring NS5A resistance-associated mutations (RAMs) have been described at baseline and after therapy failure. A mutation from glutamine to arginine at position 30 (Q30R) is a characteristic RAM for the HCV sub/genotype (GT) 1a, but arginine corresponds to the wild type in the GT-1b; still, GT-1b strains are susceptible to NS5A-inhibitors. In this study, we show that GT-1b strains with R30Q often display other specific NS5A substitutions, particularly in positions 24 and 34. We demonstrate that in GT-1b secondary substitutions usually happen after initial R30Q development in the phylogeny, and that the chemical properties of the corresponding amino acids serve to restore the positive charge in this region, acting as compensatory mutations. These findings may have implications for RAVs treatment.
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Sequence Data
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-
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