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We describe the impact of proline modifications, in our tetracyclic-indole based series of nonstructural protein 5A (NS5A) inhibitors, to their replicon profiles. This work identified NS5A inhibitors with an improved and flattened resistance profiles.
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http://dx.doi.org/10.1016/j.bmcl.2016.08.097 | 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.
Clin 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 PDFViruses
March 2025
Faculty of Medicine, University of Bergen, 5020 Bergen, Norway.
Chronic viral infections like HIV, HBV, and HCV establish persistent interactions with the host immune system, resulting in immune evasion and long-term immune dysfunction. These viruses use a range of strategies to limit host defenses, such as downregulating MHC class I, disrupting interferon signaling, altering apoptosis pathways, and suppressing cytotoxic T-cell activity. Key viral proteins, including HIV Nef, HBV X protein, and HCV NS5A, interfere with antigen presentation and JAK/STAT signaling, thereby reducing antiviral immune responses.
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