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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: These compounds had low nanomolar enzyme inhibition across HCV genotypes 1-3 and showed single digit micromolar inhibition in the HCV replicon assay and the results generated are in broad agreement with the previously proposed binding model for this compound class.
10 citations
TL;DR: The present review aims to describe the role of HCV structural and non-structural proteins in the modulation of cellular miRNA during HCV infection and pathogenesis, with a focus on the molecular mechanisms responsible for the cell re-programming involved in viral replication, immune system escape, as well as the oncogenic process.
Abstract: Hepatitis C virus (HCV) genome encodes for one long polyprotein that is processed by cellular and viral proteases to generate 10 polypeptides. The viral structural proteins include the core protein, and the envelope glycoproteins E1 and E2, present at the surface of HCV particles. Non-structural (NS) proteins consist of NS1, NS2, NS3, NS4A, NS4B, NS5a, and NS5b and have a variable function in HCV RNA replication and particle assembly. Recent findings evidenced the capacity of HCV virus to modulate host cell factors to create a favorable environment for replication. Indeed, increasing evidence has indicated that the presence of HCV is significantly associated with aberrant miRNA expression in host cells, and HCV structural and non-structural proteins may be responsible for these alterations. In this review, we summarize the recent findings on the role of HCV structural and non-structural proteins in the modulation of host cell miRNAs, with a focus on the molecular mechanisms responsible for the cell re-programming involved in viral replication, immune system escape, as well as the oncogenic process. In this regard, structural and non-structural proteins have been shown to modulate the expression of several onco-miRNAs or tumor suppressor miRNAs.
10 citations
TL;DR: It is indicated that siRNA is a potential therapeutic tool for inhibiting HCV replication and simultaneously targeting multiple viral steps with the combination of siRNAs is more effective than silencing a single target.
Abstract: Hepatitis C virus is major cause of chronic liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Presently available direct-acting antiviral drugs have improved success rate; however, high cost limits their utilization, especially in developing countries like India. In the present study, we evaluated anti-HCV potential of several siRNAs targeted against the HCV RNA-dependent RNA polymerase NS5B and cellular factors, La autoantigen, PSMA7, and human VAMP-associated protein to intercept different steps of viral life cycle. The target genes were downregulated individually as well as in combinations and their impact on viral replication was evaluated. Individual downregulation of La autoantigen, PSMA7, hVAP-A, and NS5B resulted in inhibition of HCV replication by about 67.2%, 50.7%, 39%, and 52%, respectively. However, antiviral effect was more pronounced when multiple genes were downregulated simultaneously. Combinations of siRNAs against La autoantigen with NS5B or hVAP-A resulted in greater inhibition in HCV replication. Our findings indicate that siRNA is a potential therapeutic tool for inhibiting HCV replication and simultaneously targeting multiple viral steps with the combination of siRNAs is more effective than silencing a single target.
10 citations
Patent•
27 Nov 2008
TL;DR: In this article, compositions and methods for treating an HCV infection and inhibiting HCV replication are presented, as well as methods for treatment of an infection and inhibition of replication.
Abstract: Compounds having the formula I or II wherein R1, R2, B, and V are as defined herein are Hepatitis C virus NS5b poly-merase inhibitors. Also disclosed are compositions and methods for treating an HCV infection and inhibiting HCV replication.
10 citations
TL;DR: The finding indicated that the ZINC compound 49888724 is a potential candidate to be a novel NS5B inhibitor for further design, reflecting a good binding strength and inhibitory potency than known inhibitors and the rest four ZINC compounds.
Abstract: Hepatic C virus (HCV) is a global health problem, resulting in liver cirrhosis and inflammation that can develop to hepatocellular carcinoma and fatality. The NS5B polymerase of HCV plays an important role in viral RNA replication process, making it an attractive therapeutic target for design and development of anti-HCV drugs. To search new potent compounds against the HCV NS5B polymerase, the molecular docking and the steered molecular dynamics (SMD) simulation techniques were performed. The potential potent inhibitors of the NS5B polymerase were screened out from the ZINC database using structural similarity search and molecular docking technique. Five top-hit compounds (the ZINC compounds 49888724, 49054741, 49777239, 49793673, and 49780355) were then studied by the SMD simulations based on the hypothesis that a high rupture force relates to a high binding efficiency. The results demonstrated that the ZINC compound 49888724 had a greater maximum rupture force, reflecting a good binding strength and inhibitory potency than known inhibitors and the rest four ZINC compounds. Therefore, our finding indicated that the ZINC compound 49888724 is a potential candidate to be a novel NS5B inhibitor for further design. Besides, the van der Waals interaction could be considered as the main contribution for stabilizing the NS5B-ligand complex.
10 citations