2. Academic Validation
  3. Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi® and Epclusa®

Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi® and Epclusa®

  • Bioorg Med Chem Lett. 2019 Aug 15;29(16):2415-2427. doi: 10.1016/j.bmcl.2019.04.027.
John O Link 1,  James G Taylor 2,  Alejandra Trejo-Martin 2,  Darryl Kato 2,  Ashley A Katana 2,  Evan S Krygowski 2,  Zheng-Yu Yang 2,  Sheila Zipfel 2,  Jeromy J Cottell 2,  Elizabeth M Bacon 2,  Chinh V Tran 2,  Cheng Y Yang 3,  Yujin Wang 3,  Kelly W Wang 3,  Guangyu Zhao 3,  Guofeng Cheng 4,  Yang Tian 4,  Ruoyu Gong 4,  Yu-Jen Lee 4,  Mei Yu 4,  Eric Gorman 5,  Erik Mogalian 5,  Jason K Perry 6
Affiliations

Affiliations

  • 1 Medicinal Chemistry, Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, United States. Electronic address: john.link@gilead.com.
  • 2 Medicinal Chemistry, Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, United States.
  • 3 Drug Metabolism, Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, United States.
  • 4 Biology, Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, United States.
  • 5 Formulation and Process Development, Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, United States.
  • 6 Structural Chemistry, Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, United States.
PMID: 31230974 DOI: 10.1016/j.bmcl.2019.04.027
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.

Keywords

DAA; Direct-acting-antiviral; Epclusa(®); GS-5816; HCV; Hepatitis C Virus; NS5A; Non-structural protein 5A; Rule-of-five; SVR; Single-tablet regimen; Sofosbuvir; Sustained viral response; Velpatasvir.

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