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Basic Characteristics of Mutations
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Mutation Site
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A92K |
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Mutation Site Sentence
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As shown in Fig. 1, NS5A-Y93H was found in 5 patients including 2 patients with HCV strains harboring NS5A-L28M/R30Q/Y93H mutations and NS5A-A92K in 1 patient, while NS5A-L31 was absent in all patients. |
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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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AJ238799.1;D50485.1
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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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Y |
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Treatment
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- |
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Location
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Japan |
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Literature Information
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PMID
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29892096
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Title
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Significance of NS5B Substitutions in Genotype 1b Hepatitis C Virus Evaluated by Bioinformatics Analysis
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Author
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Uchida Y,Nakamura S,Kouyama JI,Naiki K,Motoya D,Sugawara K,Inao M,Imai Y,Nakayama N,Tomiya T,Hedskog C,Brainard D,Mo H,Mochida S
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Journal
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Scientific reports
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Journal Info
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2018 Jun 11;8(1):8818
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Abstract
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To evaluate the effects of HCV NS5B amino acid substitutions on treatment outcome in Ledipasvir (LDV)/Sofosbuvir (SOF) for Japanese patients with genotype 1b HCV infection, NS5B sequences were examined in i) seven patients experiencing virologic failure after LDV/SOF in real-world practice, ii) 109 SOF-naive patients, iii) 165 patients enrolled in Phase-3 LDV/SOF trial. A218S and C316N were detected in all patients with viral relapse; the percentages of these substitutions in SOF-naive patients were 64.2% and 55.0%, respectively. Genotype 1b HCV strains with NS5B-C316N mutation were located in the leaves different from those in which HCV strains without such substitutions were present on the phylogenetic tree. Structural modeling revealed that amino acid 218 was located on the surface of the NTP tunnel. Free energy analysis based on molecular dynamics simulations demonstrated that the free energy required to pass through the tunnel was larger for triphosphate SOF than for UTP in NS5B polymerase carrying A218S, but not in wild-type. However, no susceptibility change was observed for these substitutions to SOF in replicon assay. Furthermore, the SVR rate was 100% in patients enrolled the Phase-3 trial. In conclusion, NS5B A218S and C316N were detected in all patients who relapsed following LDV/SOF in real-world practice. These substitutions did not impact the overall SVR rate after LDV/SOF, however, further studies are needed to elucidate the impact of these substitutions.
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Sequence Data
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LC210145-LC210252;LC216928-LC216934
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