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NS5B

About: NS5B is a research topic. Over the lifetime, 1314 publications have been published within this topic receiving 59534 citations.


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Journal ArticleDOI
TL;DR: Post-treatment RASs in hepatitis C virus appear by 2 mechanisms: the selection of pre-existing substitutions among quasispecies and the generation of novel mutations during therapy.
Abstract: Resistance-associated substitutions (RASs) in hepatitis C virus (HCV) appear upon failure of treatment with direct-acting antivirals (DAAs). However, their origin has not been clarified in detail. Among 11 HCV genotype 1b patients who experienced virologic failure with asunaprevir (ASV)/daclatasvir (DCV), 10 had major NS5A L31M/V-Y93H variants after treatment. L31M/V-Y93H variants were detected as a minor clone before therapy in 6 patients and were the most closely related to the post-treatment variants by phylogenetic tree analysis in 4 patients. Next, to consider the involvement of a trace amount of pre-existing variants below the detection limit, we analysed human hepatocyte chimeric mice infected with DAA-naive patient serum. L31V-Y93H variants emerged after treatment with ledipasvir (LDV)/GS-558093 (nucleotide NS5B inhibitor) and decreased under the detection limit, but these variants were dissimilar to the L31V-Y93H variants reappearing after ASV/DCV re-treatment. Finally, to develop an infection derived from a single HCV clone, we intrahepatically injected full-genome HCV RNA (engineered based on the wild-type genotype 1b sequence) into chimeric mice. A new Y93H mutation actually occurred in this model after LDV monotherapy failure. In conclusion, post-treatment RASs appear by 2 mechanisms: the selection of pre-existing substitutions among quasispecies and the generation of novel mutations during therapy.

25 citations

Journal ArticleDOI
TL;DR: Structural and immunological computational studies showed that the fliC-NT300 can be introduced as a prophylactic or therapeutic candidate vaccine against the HCV, after the efficacy of that was confirmed via in vitro and in vivo assays.
Abstract: Hepatitis C virus (HCV) infection is a major global issue that leads to serious liver disease such as chronic liver inflammation and hepatocellular carcinoma. At present, no approved vaccine is available for control or treatment of HCV infection. Therefore, the development of an efficient vaccine against HCV is an urgent need. Today, designing an effective vaccine against hepatitis C is one of the outmost propriety for researchers. Fusion protein vaccines containing the immunogen proteins and adjuvant molecules are able to stimulate both humoral and cellular responses that are crucial for eradicating HCV infection. Herein, in silico design of fusion forms of vaccine candidates against HCV, including flagellin (fliC) from Pseudomonas aeruginosa and NS5B antigen (NT300) from HCV was performed. First, two forms of fusion protein (NT300-fliC and fliC-NT300) were designed and analyzed using different bioinformatics tools. For this aim, the Iterative threading assembly refinement (I-TASSER) server was used for modeling the fusion forms of protein; namely, NT300-fliC and fliC-NT300, then the high-rank 3D model of fusion protein was selected, subsequently various physico-chemical, and structural parameters were examined bioinformatically. After the selection of the best construct (fliC-NT300), the interaction of flagellin part of vaccine with toll-like receptor 5 (TLR5) was evaluated via docking studies. Our results represented that based on data obtained from various servers, and the docking analyses of two constructs, fliC-NT300 fusion form showed better results than NT300-fliC. For this reason, the fliC-NT300 form was selected for further evaluations. In sum, structural and immunological computational studies showed that the fliC-NT300 can be introduced as a prophylactic or therapeutic candidate vaccine against the HCV, after the efficacy of that was confirmed via in vitro and in vivo assays.

25 citations

Journal ArticleDOI
01 Aug 2003-Virology
TL;DR: The GB virus-B (GBV-B) nonstructural protein 5B (NS5B) encodes an RNA-dependent RNA polymerase (RdRp) with greater than 50% sequence similarity to the hepatitis C virus (HCV) NS5B, which may represent a relevant surrogate system for testing HCV antiviral agents.

25 citations

Journal ArticleDOI
TL;DR: Compound 33, an arylidene derivative, was found to be the most active compound in this series with an IC50 value of 25.3 µM, and molecular docking studies were performed on the thumb pocket‐II of NS5B to postulate the binding mode for these compounds.
Abstract: In continuation of our efforts to develop new derivatives as hepatitis C virus (HCV) NS5B inhibitors, we synthesized novel 5-arylidene-4-thiazolidinones. The novel compounds 29–42, together with their synthetic precursors 22–28, were tested for HCV NS5B inhibitory activity; 12 of these compounds displayed IC50 values between 25.3 and 54.1 µM. Compound 33, an arylidene derivative, was found to be the most active compound in this series with an IC50 value of 25.3 µM. Molecular docking studies were performed on the thumb pocket-II of NS5B to postulate the binding mode for these compounds.

25 citations

Journal ArticleDOI
TL;DR: This review focuses on hepatitis C protease and polymerase inhibitors that have progressed to phase II clinical development, foreshadowing the era of STAT-Cs.
Abstract: Since the discovery of the hepatitis C virus (HCV) as the major cause of non-A, non-B hepatitis in 1989, the search for specific targeted antiviral therapy for HCV (STAT-C) has been underway Recently, major advances in the understanding of HCV biology and the development of an in vitro system of HCV replication have contributed to the selection of multiple candidate drugs for the treatment of hepatitis C In 2006, five such candidate drugs have entered phase II clinical trials in patients chronically infected with hepatitis C, including small molecule inhibitors of the HCV NS3 serine protease and NS5B RNA-dependent RNA polymerase This review focuses on hepatitis C protease and polymerase inhibitors that have progressed to phase II clinical development, foreshadowing the era of STAT-Cs

25 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202310
202258
202128
202033
201943
201842