Results 151 to 160 of about 9,676 (179)

Discovery of potent macrocyclic HCV NS5A inhibitors

Bioorganic & Medicinal Chemistry Letters, 2016
HCV NS5A inhibitors have demonstrated impressive in vitro virologic profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed-dose combination (FDC) regimen for the treatment of HCV infection.
Wensheng Yu, Bancha Vibulbhan, Stuart B. Rosenblum, Gregory S. Martin, A. Samuel Vellekoop, Christian L. Holst, Craig A. Coburn, Michael Wong, Oleg Selyutin, Tao Ji, Bin Zhong, Bin Hu, Lei Chen, Michael P. Dwyer, Yueheng Jiang, Anilkumar G. Nair, Ling Tong, Qingbei Zeng, Sony Agrawal, Donna Carr, Laura Rokosz, Rong Liu, Stephanie Curry, Patricia McMonagle, Paul Ingravallo, Fred Lahser, Ernest Asante-Appiah, James Fells, Joseph A. Kozlowski   +28 more
openaire   +2 more sources

Targeting the NS5A protein of HCV: An emerging option

Drugs of the Future, 2011
Hepatitis C virus (HCV) infects more than 3% of the world's population, leading to an increased risk of cirrhosis and hepatocellular carcinoma. The current standard of care, a combination of pegylated interferon alfa and ribavirin, is poorly tolerated and often ineffective against the most prevalent genotype of the virus, genotype 1.
D G, Cordek, J T, Bechtel, A T, Maynard, W M, Kazmierski, C E, Cameron   +4 more
openaire   +2 more sources

Ser38‐His93‐Asn91 triad confers resistance of JFH1 HCV NS5A‐Y93H variant to NS5A inhibitors

The FEBS Journal
HCV NS5A is a dimeric phosphoprotein involved in HCV replication. NS5A inhibitors are among direct‐acting antivirals (DAA) for HCV therapy. The Y93H mutant of NS5A is resistant to NS5A inhibitors, but the precise mechanism remains unclear. In this report, we proposed a Ser38‐His93‐Asn91 triad to dissect the mechanism. Using
Wei‐Ping Lee, Keng‐Chang Tsai, Shi‐Xian Liao, Yi‐Hsiang Huang, Ming‐Chih Hou, Keng‐Hsin Lan   +5 more
openaire   +2 more sources

The Domain 2 of the HCV NS5A Protein is Intrinsically Unstructured

Protein and Peptide Letters, 2010
We present here our current understanding of the NS5A-D2 domain of the hepatitis C virus. Whereas this protein domain is globally unstructured as assessed by macroscopic techniques such as size exclusion chromatography, circular dichroism and homonuclear NMR spectroscopy, high resolution triple resonance spectroscopy allows the identification of a ...
Hanoulle, Xavier, Badillo, Aurelie, Verdegem, Dries, Penin, François, Lippens, Guy   +4 more
openaire   +3 more sources

Differential Sensitivity of 5′UTR-NS5A Recombinants of Hepatitis C Virus Genotypes 1−6 to Protease and NS5A Inhibitors

Gastroenterology, 2014
Hepatitis C virus (HCV) therapy will benefit from the preclinical evaluation of direct-acting antiviral (DAA) agents in infectious culture systems that test the effects on different virus genotypes. We developed HCV recombinants comprising the 5' untranslated region-NS5A (5-5A) from genotypes 1-6 and 2a(JFH1) NS5B-3' untranslated region, and tested the
Li, Yi-Ping, Ramirez, Santseharay, Humes, Daryl, Jensen, Sanne B, Gottwein, Judith M, Bukh, Jens   +5 more
openaire   +3 more sources

Recombinant HCV Variants With NS5A From Genotypes 1–7 Have Different Sensitivities to an NS5A Inhibitor but Not Interferon-α

Gastroenterology, 2011
Heterogeneity in the hepatitis C virus (HCV) protein NS5A influences its sensitivity to interferon-based therapy. Furthermore, NS5A is an important target for development of HCV-specific inhibitors. We aimed to develop recombinant infectious cell culture systems that express NS5A from isolates of the 7 major HCV genotypes, and determining their ...
Scheel, Troels K H, Gottwein, Judith M, Mikkelsen, Lotte S, Jensen, Tanja B, Bukh, Jens   +4 more
openaire   +3 more sources

The effect of classical swine fever virus NS5A and NS5A mutants on oxidative stress and inflammatory response in swine testicular cells

Research in Veterinary Science, 2017
Infection with classical swine fever virus (CSFV) results in highly significant economic losses; this infection is characterized by being highly contagious and accompanied by hyperthermia and systemic bleeding. Oxidative stress (OS) plays a critical role in the pathological process of viral infection. The function of the nonstructural protein 5A (NS5A)
Wang, Dong, Huifang, Lv, Yifan, Wang, Xiaomeng, Li, Cheng, Li, Lu, Wang, Chengbao, Wang, Kangkang, Guo, Yanming, Zhang   +8 more
openaire   +2 more sources

NS5A as a Target for HCV Drug Discovery

2019
Discovery and development of HCV inhibitors is one of the most successful stories in the history of antiviral research. After more than 30 years of effort by academic and pharmaceutical researchers, HCV infection is a curable disease. In fact, HCV is the first chronic infectious disease to be cured with combinations of direct antiviral agents.
Donald R. O’Boyle, Min Gao
openaire   +1 more source

HCV NS5A Inhibitors: The Devil Is in the Details

Gastroenterology, 2014
Menashe, Elazar, Jeffrey S, Glenn
openaire   +2 more sources

Dimer Organization of Membrane‐Associated NS5A of Hepatitis C Virus as Determined by Highly Sensitive 1H‐Detected Solid‐State NMR

Angewandte Chemie - International Edition, 2021
Vlastimil Jirásko, Alons Lends, Nils-Alexander Lakomek   +2 more
exaly