A review on HCV inhibitors: Significance of non-structural polyproteins

Abstract

a b s t r a c tHepatitis C virus (HCV) mortality and morbidity is a world health misery with an approximate 130e150 million chronically HCV tainted and suffering individuals and it initiate critical liver malfunction like cirrhosis, hepatocellular carcinoma or liver HCV cancer. HCV NS5B protein one of the best studied therapeutic target for the identification of new drug candidates to be added to the combination or multiple combination medication recently approved. During the past few years, NS5B has thus been an important object of attractive medicinal chemistry endeavors, which induced to the surfacing of betrothal preclinical drug molecules. In this scenario, the current review set limit to discuss research published on NS5B and few other therapeutic functional inhibitors concentrating on hit investigation, hit to lead optimization, ADME parameters evaluation, and the SAR data which was out for each compound type and similarity taken into consideration. The discussion outlined in this specific review will surly helpful and vital tool for those medicinal chemists investigators working with HCV research programs mainly pointing on NS5B and set broad spectrum identification of creative anti HCV compounds. This mini review also tells each and every individual compound ability related how much they are active against NS5B and few other targets.

A “Deep Dive” into the SARS-Cov-2 Polymerase Assembly: Identifying Novel Allosteric Sites and Analyzing the Hydrogen Bond Networks and Correlated Dynamics

“…The existence of such allosteric sites is supported by our findings (see results) as well as by earlier lessons from similar RNA viruses (e.g. the HCV polymerase has four druggable allosteric sites in addition to its active site [16][17] ). The need to identify more druggable binding sites within the SARS-CoV-2 replicase machinery is highly desirable as targeting only the active site of the polymerase with nucleoside analogs (NA)s may not prove enough to fully inhibit viral replication.…”

A ‘deep dive’ into the SARS-Cov-2 polymerase assembly: identifying novel allosteric sites and analyzing the hydrogen bond networks and correlated dynamics

“…The existence of such allosteric sites is supported by our findings (see below) as well as by earlier lessons from similar RNA viruses (e.g. the HCV polymerase has four druggable allosteric sites in addition to its active site (Ganta et al, 2019;Li & Shi, 2010). The recent SARS-CoV-2 polymerase cryo-EM structures (Gao et al, 2020;Yin et al, 2020) provide a unique opportunity to construct an accurate model for this complex.…”

Insight into the drug resistance mechanisms of GS-9669 caused by mutations of HCV NS5B polymerase via molecular simulation

“…Hepatitis C virus (HCV), an enveloped (+)-strand RNA virus, primarily affects the liver and may lead to liver Cirrhosis and carcinoma [1] , [2] . The HCV is mainly transmitted to people through blood, mother-to-child, and sexual contact [3] , [4] .…”