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Basic Characteristics of Mutations
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Mutation Site
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E327D |
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Mutation Site Sentence
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It was found that K304R (82.4%), E327D and P300T (76.5% each) substitutions were the most distributed in the tested samples, respectively. |
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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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NS5B |
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Standardized Encoding Gene
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NS5B
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Genotype/Subtype
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- |
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Viral Reference
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DQ988074;FJ839870;FJ462440;D17763;AM910652
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Functional Impact and Mechanisms
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Disease
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Hepatitis C, Chronic
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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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Egypt |
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Literature Information
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PMID
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33857212
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Title
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Distribution of naturally -occurring NS5B resistance-associated substitutions in Egyptian patients with chronic Hepatitis C
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Author
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Ahmed HR,Waly NGFM,Abd El-Baky RM,Yahia R,Hetta HF,Elsayed AM,Ibrahem RA
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Journal
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PloS one
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Journal Info
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2021 Apr 15;16(4):e0249770
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Abstract
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BACKGROUND: NS5B polymerase inhibitors represent the cornerstone of the present treatment of Hepatitis C virus infection (HCV). Naturally occurring substitution mutations to NS5B inhibitors have been recorded. The current study intended to demonstrate possible natural direct acting antiviral (DAA)-mutations of the HCV NS5B region in HCV patients in Minia governorate, Egypt. METHODS: Samples were collected from 27 treatment-naive HCV patients and 8 non-responders. Out of 27 treatment-naive patients, 17 NS5B sequences (amino acids 221-345) from treatment-naive patients and one sample of non-responders were successfully amplified. Nucleotide sequences have been aligned, translated into amino acids, and compared to drug resistance mutations reported in the literature. RESULTS: NS5B amino acid sequence analysis ensures several novel NS5B mutations existence (more than 40 substitution mutations) that have not been previously documented to be correlated with a resistant phenotype. It was found that K304R (82.4%), E327D and P300T (76.5% each) substitutions were the most distributed in the tested samples, respectively. S282T, the major resistance mutation that induces high sofosbuvir-resistance level in addition to other reported mutations (L320F/C) and (C316Y/N) were not recognized. Q309R mutation is a ribavirin-associated resistance, which was recognized in one strain (5.9%) of genotype 1g sequences. Besides, one substitution mutation (E237G) was identified in the successfully amplified non-responder sample. CONCLUSION: Our study showed various combinations of mutations in the analyzed NS5B genes which could enhance the possibility of therapy failure in patients administered regimens including multiple DAA.
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Sequence Data
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MN794403;MN894516;MN794406;MN794404;MN794405;MN794407;MN794408;MN794409;MN794410;MN794411;MN794412;MN894517;MN794413;MN794414;MN794415;MN794416;MN794417;MW307936
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