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Basic Characteristics of Mutations
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Mutation Site
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S98G |
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Mutation Site Sentence
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We observed a novel substitution at NS5A amino acid residue 98 [serine to glycine (S98G)] in patients who relapsed post-treatment. |
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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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3 |
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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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Daclatasvir (DCV) |
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Location
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Brazil |
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Literature Information
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PMID
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33141008
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Title
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A novel substitution in NS5A enhances the resistance of hepatitis C virus genotype 3 to daclatasvir
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Author
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Fernandes Campos GR,Ward J,Chen S,Bittar C,Vilela Rodrigues JP,Martinelli ALC,Souza FF,Pereira LRL,Rahal P,Harris M
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Journal
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The Journal of general virology
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Journal Info
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2021 Jan;102(1):jgv001496
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Abstract
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Hepatitis C virus (HCV) genotype 3 presents a high level of both baseline and acquired resistance to direct-acting antivirals (DAAs), particularly those targeting the NS5A protein. To understand this resistance we studied a cohort of Brazilian patients treated with the NS5A DAA, daclatasvir and the nucleoside analogue, sofosbuvir. We observed a novel substitution at NS5A amino acid residue 98 [serine to glycine (S98G)] in patients who relapsed post-treatment. The effect of this substitution on both replication fitness and resistance to DAAs was evaluated using two genotype 3 subgenomic replicons. S98G had a modest effect on replication, but in combination with the previously characterized resistance-associated substitution (RAS), Y93H, resulted in a significant increase in daclatasvir resistance. This result suggests that combinations of substitutions may drive a high level of DAA resistance and provide some clues to the mechanism of action of the NS5A-targeting DAAs.
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Sequence Data
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-
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