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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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TL;DR: This study uses molecular dynamics simulations to understand the structural and dynamic changes that result when inhibitors are bound at three different allosteric binding sites on the enzyme, and observes that ligand binding at each site alters the structure and dynamics of NS5B in a distinct manner.
11 citations
TL;DR: In this article, the authors summarized the viral and cellular factors involved in regulating hepatitis C virus genomic RNA replication and the DAAs that inhibit HCV replication and proposed direct-acting antivirus (DAAs) targeting the replication complex.
Abstract: The life cycle of the hepatitis C virus (HCV) can be divided into several stages, including viral entry, protein translation, RNA replication, viral assembly, and release. HCV genomic RNA replication occurs in the replication organelles (RO) and is tightly linked to ER membrane alterations containing replication complexes (proteins NS3 to NS5B). The amplification of HCV genomic RNA could be regulated by the RO biogenesis, the viral RNA structure (i.e., cis-acting replication elements), and both viral and cellular proteins. Studies on HCV replication have led to the development of direct-acting antivirals (DAAs) targeting the replication complex. This review article summarizes the viral and cellular factors involved in regulating HCV genomic RNA replication and the DAAs that inhibit HCV replication.
11 citations
TL;DR: It is found that mutations predicted to alter miR-122 binding at the IRES and NS5B.2 sites lead to reductions in HCV core protein expression and viral RNA accumulation; with a concomitant decrease in viral particle production for the NS5 B.2 mutant.
Abstract: Hepatitis C virus (HCV) recruits two molecules of the liver-specific microRNA-122 (miR-122) to two adjacent sites (S1 and S2) located at the 5' end of the viral RNA genome. This interaction promotes HCV RNA accumulation by stabilising the viral RNA and resulting in alteration of the secondary structure of the viral genome. In addition to S1 and S2, the HCV genome contains several other putative miR-122 binding sites, one in the IRES region, three in the NS5B coding region, and one in the 3' UTR. We investigated and compared the relative contributions of the S1, S2, IRES, NS5B (NS5B.1, 2 and 3) and 3' UTR sites on protein expression, viral RNA accumulation, and infectious particle production by mutational analysis and supplementation with compensatory mutant miR-122 molecules. We found that mutations predicted to alter miR-122 binding at the IRES and NS5B.2 sites lead to reductions in HCV core protein expression and viral RNA accumulation; with a concomitant decrease in viral particle production for the NS5B.2 mutant. However, supplementation of miR-122 molecules with compensatory mutations did not rescue these site mutants to wild-type levels, suggesting that mutation of these sequences likely disrupts an additional interaction important to the HCV life cycle, beyond direct interactions with miR-122. Thus, S1 and S2 play a predominant role in viral RNA accumulation, while miR-122 interactions with the IRES, NS5B and 3' UTR regions have negligible contributions to viral protein expression, viral RNA accumulation, and infectious particle production.
11 citations
TL;DR: Se sequencing in the core region is preferable for genotyping specimens, even though longer PCR products are required as this method enables discrimination between genotype 6a and the remaining genotypes.
Abstract: Objective: The present study was performed to genotype hepatitis C virus (HCV) by direct sequencing of a 222-bp nucleotide in the NS5B region and comparing the results with those of
11 citations
TL;DR: Ribonucleoside phosphonate analogues containing 2'-α-fluoro modifications were synthesized and their potency evaluated against HCV RNA polymerase, showing only modest cell-based activity in the HCV replicon.
11 citations