NS5B

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

The Second-generation of Highly Potent Hepatitis C Virus (HCV) NS3/4A Protease Inhibitors: Evolutionary Design Based on Tailor-made Amino Acids, Synthesis and Major Features of Bio-activity.

Abstract: Hepatitis C is a current pandemic liver disease caused by the hepatitis C virus (HCV) with high morbidity and mortality Recently, the direct-acting antiviral agents (DAAs) targeting HCV NS3/4A, NS5A and NS5B have become the most effective therapies against HCV infection in the clinical treatment Among them, the second-generation of NS3/4A inhibitors have emerged as the mainstay of the DAA therapies, which are derived from the peptide substrate of NS3/4A protease and modified with various tailor-made amino acids in order to achieve high sustained virologic response (SVR) against HCV This review summarizes sixteen examples of the second-generation of HCV NS3/4A inhibitors, mainly focusing on the clinical application, structure development, structure-activity relationship (SAR) and their synthesis

Mangosteen xanthones suppress hepatitis C virus genome replication

Abstract: Hepatitis C virus (HCV) is a hepatotropic single-stranded RNA virus. HCV infection is causally linked with development of liver cirrhosis and hepatocellular carcinoma. Enhanced production of reactive oxygen species by HCV has been implicated to play an important role in HCV-induced pathogenesis. Mangosteen has been widely used as a traditional medicine as well as a dietary supplement ,thanks to its powerful anti-oxidant effect. In the present study, we demonstrated that the ethanol extract from mangosteen fruit peels (MG-EtOH) is able to block HCV genome replication using HCV genotype 1b Bart79I subgenomic (EC50 5.1 μg/mL) and genotype 2a J6/JFH-1 infectious replicon systems (EC50 3.8 μg/mL). We found that inhibition of HCV replication by MG-EtOH led to subsequent down-regulation of expression of HCV proteins. Interestingly, MG-EtOH exhibited a modest inhibitory effect on in vitro RNA polymerase activity of NS5B. Among a number of xanthones compounds identified within this MG-EtOH, we discovered α-MG (EC50 6.3 μM) and γ-MG (EC50 2.7 μM) as two major single molecules responsible for suppression of HCV replication. This finding will provide a valuable molecular basis to further develop mangosteen as an important dietary supplement to combat HCV-induced liver diseases.

A zebrafish model for subgenomic hepatitis C virus replication.

Abstract: Persistent infection with hepatitis C virus (HCV) is a major risk factor in the development of hepatocellular carcinoma The elucidation of the pathogenesis of HCV-associated liver disease is hampered by the absence of an appropriate small animal model Zebrafish exhibits high genetic homology to mammals, and is easily manipulated experimentally In this study, we describe the use of a zebrafish model for the analysis of HCV replication mechanisms As the 5' untranslated region (UTR), the core protein, the non-structural protein 5B (NS5B) and the 3'UTR are essential for HCV replication, we constructed a HCV sub-replicon gene construct including the 4 gene sequences and the enhanced green fluorescent protein (EGFP) reporter gene; these genes were transcribed through the mouse hepatocyte nuclear factor 4 (mHNF4) promoter By microinjection of the subgenomic replicon vector into zebrafish larvae, the virus was easily detected by observing EGFP fluorescence in the liver The positive core and NS5B signals showed positive expression of the HCV gene construct in zebrafish by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis Importantly, the negative strand sequence of the HCV subgenomic RNA was detected by RT-PCR and hybridization in situ, demonstrating that the HCV sub-replicon has positive replication activity Furthermore, the hybridization signal mainly appeared in the liver region of larvae, as detected by the sense probe of the core protein or NS5B, which confirmed that the sub-replicon amplification occurred in the zebrafish liver The amplification of the sub-replicon caused alterations in the expression of certain genes, which is similar to HCV infection in human liver cells To verify the use of this zebrafish model in drug evaluation, two drugs against HCV used in clinical practice, ribavirin and oxymatrine, were tested and these drugs showed significant inhibition of replication of the HCV sub-replicon in the larvae In conclusion, this zebrafish model of HCV may prove to be a novel and simple in vivo model for the study of the mechanisms of HCV replication and may also prove useful in the disovery of new anti-HCV drugs