Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi® and Epclusa®. Issue 16 (15th August 2019)

• Record Type: Journal Article
• Authors: Link, John O.; Taylor, James G.; Trejo-Martin, Alejandra; Kato, Darryl; Katana, Ashley A.; Krygowski, Evan S.; Yang, Zheng-Yu; Zipfel, Sheila; Cottell, Jeromy J.; Bacon, Elizabeth M.; Tran, Chinh V.; Yang, Cheng Y.; Wang, Yujin; Wang, Kelly W.; Zhao, Guangyu; Cheng, Guofeng; Tian, Yang; Gong, Ruoyu; Lee, Yu-Jen; Yu, Mei; Gorman, Eric; Mogalian, Erik; Perry, Jason K.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 16(2019)
• Page Start: 2415
• Page End: 2427
• Publication Date: 2019-08-15
• Subjects: HCV -- Hepatitis C Virus -- Non-structural protein 5A -- NS5A -- Sustained viral response -- SVR -- Direct-acting-antiviral -- DAA -- Rule-of-five -- Single-tablet regimen -- Velpatasvir -- GS-5816 -- Epclusa® -- Sofosbuvir; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.04.027
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa ®, an STR with 98% cure-rates for genotype 1–6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi ®, which affords 97% cure-rates for genotype 1–6 HCV patients who have previously failed another treatment regimen.