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Synthesis of deuterated S-217622 (Ensitrelvir) with antiviral activity against coronaviruses including SARS-CoV-2.
Yang, Yujian; Cao, Liu; Yan, Ming; Zhou, Jun; Yang, Sidi; Xu, Tiefeng; Huang, Siyao; Li, Kun; Zhou, Qifan; Li, Guanguan; Zhu, Yujun; Cong, Feng; Zhang, Hongmin; Guo, Deyin; Li, Yingjun; Zhang, Xumu.
  • Yang Y; Department of Chemistry, College of Science, Academy for Advanced Interdisciplinary Studies, and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong, 518000, China.
  • Cao L; Centre for Infection and Immunity Studies (CIIS), School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China.
  • Yan M; Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong, 518000, China.
  • Zhou J; Department of Chemistry, College of Science, Academy for Advanced Interdisciplinary Studies, and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong, 518000, China.
  • Yang S; Guangzhou Laboratory, Bio-island, Guangzhou, Guangdong, 510320, China.
  • Xu T; Centre for Infection and Immunity Studies (CIIS), School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China.
  • Huang S; Centre for Infection and Immunity Studies (CIIS), School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China.
  • Li K; Centre for Infection and Immunity Studies (CIIS), School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China.
  • Zhou Q; Department of Chemistry, College of Science, Academy for Advanced Interdisciplinary Studies, and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong, 518000, China.
  • Li G; Department of Chemistry, College of Science, Academy for Advanced Interdisciplinary Studies, and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong, 518000, China.
  • Zhu Y; Guangdong Province Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, Guangdong, 510663, China.
  • Cong F; Guangdong Province Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, Guangdong, 510663, China.
  • Zhang H; Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong, 518000, China. Electronic address: zhanghm@sustech.edu.cn.
  • Guo D; Centre for Infection and Immunity Studies (CIIS), School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China; Guangzhou Laboratory, Bio-island, Guangzhou, Guangdong, 510320, China. Electronic address: guodeyin@mail.sysu.edu.cn.
  • Li Y; Department of Chemistry, College of Science, Academy for Advanced Interdisciplinary Studies, and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong, 518000, China. Electronic address: liyj@sustech.edu.cn.
  • Zhang X; Department of Chemistry, College of Science, Academy for Advanced Interdisciplinary Studies, and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong, 518000, China. Electronic address: zhangxm@sustech.edu.cn.
Antiviral Res ; 213: 105586, 2023 05.
Article in English | MEDLINE | ID: covidwho-2287615
ABSTRACT
S-217622 (Ensitrelvir) is a reversible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3-chymotrypsin-like protease (3CLpro) inhibitor which obtained emergency regulatory approval in Japan for the treatment of SARS-CoV-2 infection on Nov 22, 2022. Herein, analogs of S-271622 with deuterium-for-hydrogen replacement were synthesized for comparison of the antiviral activities and pharmacokinetic (PK) profiles. Compared to the parent compound, C11-d2-S-217622 compound YY-278 retained in vitro activity against 3CLpro and SARS-CoV-2. X-ray crystal structural studies showed similar interactions of SARS-CoV-2 3CLpro with YY-278 and S-271622. The PK profiling revealed the relatively favorable bioavailability and plasma exposure of YY-278. In addition, YY-278, as well as S-217622, displayed broadly anti-coronaviral activities against 6 other coronaviruses that infect humans and animals. These results laid the foundation for further research on the therapeutic potential of YY-278 against COVID-19 and other coronaviral diseases.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Animals / Humans Country/Region as subject: Asia Language: English Journal: Antiviral Res Year: 2023 Document Type: Article Affiliation country: J.antiviral.2023.105586

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Animals / Humans Country/Region as subject: Asia Language: English Journal: Antiviral Res Year: 2023 Document Type: Article Affiliation country: J.antiviral.2023.105586