98%
921
2 minutes
20
A series of symmetrical E-stilbene prolinamides that originated from the library-synthesized lead 3 was studied with respect to HCV genotype 1a (G-1a) and genotype 1b (G-1b) replicon inhibition and selectivity against BVDV and cytotoxicity. SAR emerging from an examination of the prolinamide cap region revealed 11 to be a selective HCV NS5A inhibitor exhibiting submicromolar potency against both G-1a and G-1b replicons. Additional structural refinements resulted in the identification of 30 as a potent, dual G-1a/1b HCV NS5A inhibitor.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1021/jm301796k | DOI Listing |
PLoS Pathog
September 2025
Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.
Hepatitis C virus (HCV) exhibits a narrow species tropism, causing robust infections only in humans and experimentally inoculated chimpanzees. While many host factors and restriction factors are known, many more likely remain unknown, which has limited the development of mouse or other small animal models for HCV. One putative restriction factor, the black flying fox orthologue of receptor transporter protein 4 (RTP4), was previously shown to potently inhibit viral genome replication of several ER-replicating RNA viruses.
View Article and Find Full Text PDFSci Rep
July 2025
School of basic Medicine, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, 150040, China.
This study employs structural bioinformatics approaches to identify and evaluate potential drug targets within the Hepatitis C virus (HCV) proteome. Through integration of homology modeling, molecular docking, and molecular dynamics simulations, we analyzed the structural features and druggability of key HCV proteins. The research focused on predicting binding sites, evaluating protein-ligand interactions, and assessing the therapeutic potential of identified targets.
View Article and Find Full Text PDFJ Clin Exp Hepatol
May 2025
Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
Background: The National Viral Hepatitis Control Program (NVHCP) has a cure rate of 91.6% when using direct-acting antivirals (DAAs)-sofosbuvir with an NS5A inhibitor (ledipasvir, daclatasvir or velpatasvir) ± ribavirin in the Punjab hub-and-spoke model of hepatitis C virus (HCV) elimination.
Methods: We collected the clinical and virological data for the ∼8.
Arch Virol
May 2025
Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, El-Sadat City, Menoufia Governate, Egypt.
Hepatitis C virus (HCV) infection is a significant global health concern, as both acute and chronic hepatitis caused by HCV can lead to liver cancer and long-term liver damage. Thymoquinone (TQ), the active compound found in the remarkable herb Nigella sativa, has various anti-inflammatory and antiproliferative effects. In this study, we investigated the effect of TQ on the interferon-alpha (IFN-α) pathway and its ability to prevent HCV replication in the HepG2 cell line.
View Article and Find Full Text PDFClin Pharmacol Drug Dev
June 2025
Department of Clinical Development at Atea Pharmaceuticals, Inc., Boston, MA, USA.
A combination of nucleotide hepatitis C virus (HCV) nonstructural protein (NS) 5B and 5A inhibitors is a preferred standard of care for treating chronic HCV. Bemnifosbuvir is a novel oral guanosine nucleotide prodrug with potent pan-genotypic inhibitory activity against HCV NS5B. Ruzasvir, a small-molecule NS5A inhibitor, has demonstrated improved anti-HCV activity compared with first-generation NS5A inhibitors.
View Article and Find Full Text PDF