The RNA-dependent RNA polymerase from the Hepatitis C Virus (gene product NS5B) is a validated drug target because of its critical role in genome replication. There are at least four distinct allosteric sites on the polymerase to which several small molecule inhibitors bind. In addition, numerous crystal structures have been solved with different allosteric inhibitors bound to the polymerase. H...

Resistance to direct-acting antiviral (DAA) agents against hepatitis C virus (HCV) infection is driven by the selection of mutations at different positions in the NS3 protease, NS5B polymerase and NS5A proteins. With the exception of NS5B nucleos(t)ide inhibitors, most DAAs possess a low genetic barrier to resistance, with significant cross-resistance between compounds belonging to the same fam...

BACKGROUND/AIM The frequency of genotype 4 hepatitis C virus (HCV) infections is significantly higher in Kayseri compared to other provinces in Turkey. We aimed to characterize genotype 4 infections in Kayseri by analyzing the demographic and laboratory data of218 HCV RNA-positive, treatment-naive patients admitted to the Kayseri Training and Research Hospital in 2010 and 2011. MATERIALS AND ...

To evaluate the capacity of Versant HCV genotype assay (LiPA) 2.0 to identify hepatitis C virus (HCV) genotypes, 110 serum samples were collected from chronic hepatitis C patients. Three methods were compared: core sequence analysis, NS5B sequence analysis and the INNO-LiPA assay. The result showed that 102 (92.7%) of the samples were amplified in either or both regions, of which 97 were amplif...

Treatment of hepatitis C virus (HCV) infection has been met with less than satisfactory results due primarily to its resistance to and significant side effects from alpha interferon (IFN-alpha). New classes of safe and broadly acting treatments are urgently needed. Cyclosporine (CsA), an immunosuppressive and anti-inflammatory drug for organ transplant patients, has recently been shown to be hi...

We evaluated the transition of dominant resistance-associated substitutions (RASs) in hepatitis C virus during long-term follow-up after the failure of DAAs (direct acting antivirals)-based therapy. RASs in non-structure (NS)3/4A, NS5A, NS5B, and deletions in NS5A from 20 patients who failed simeprevir/pegylated-interferon/ribavirin (SMV/PEG-IFN/RBV) and 25 patients who failed daclatasvir/asuna...

Hepatitis C virus (HCV) is a positive-sense single-stranded RNA virus. NS5b is an RNA-dependent RNA polymerase that polymerizes the newly synthesized RNA. HCV likely uses host proteins for its replication, similar to other RNA viruses. To identify the cellular factors involved in HCV replication, we searched for cellular proteins that interact with the NS5b protein. HnRNP A1 and septin 6 protei...

The replication of the hepatitis C viral (HCV) genome is accomplished by the NS5B RNA-dependent RNA polymerase (RdRp), for which mechanistic understanding and structure-guided drug design efforts have been hampered by its propensity to crystallize in a closed, polymerization-incompetent state. The removal of an autoinhibitory β-hairpin loop from genotype 2a HCV NS5B increases de novo RNA synthe...

Denaturing gradient gel electrophoresis (DGGE) was used to study the diversity of hepatitis C virus (HCV) quasispecies. Optimized DGGE running conditions were applied to screen for variations in sequences cloned from amplicons originating from the nonstructural 5b (NS5b) gene of HCV in blood of hemophilia patients, intravenous drug users, and blood donors (five specimens from each study group, ...

The enzymes involved in the replication of the Hepatitis C Virus (HCV) have been some of the most intensely studied proteins in recent history because they are targets for rational drug design. HCV is an established and growing menace to human health that is without a current vaccine or a widely affordable and effective treatment. Traditional antiviral screening is difficult with HCV because of...