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Identification and semisynthesis of (-)-anisomelic acid as oral agent against SARS-CoV-2 in mice.
Yu, Hai-Xin; Zheng, Nan; Yeh, Chi-Tai; Lee, Chien-Ming; Zhang, Qi; Zheng, Wen-Lv; Chang, Qing; Li, Yuan-He; Li, Yu-Jun; Wu, Gui-Zhen; Quan, Jun-Min; Zhang, Lin-Qi; Tzeng, Yew-Min; Yang, Zhen.
  • Yu HX; Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
  • Zheng N; Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
  • Yeh CT; Department of Medicinal Research and Education, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan.
  • Lee CM; Department of Applied Science, Taitung University, Taitung 95092, Taiwan.
  • Zhang Q; Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center, and Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing 100084, China.
  • Zheng WL; Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
  • Chang Q; Lanzhou Institute of Separation Science, Lanzhou 730013, China.
  • Li YH; State Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education and Beijing National Laboratory for Molecular Science (BNLMS), College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
  • Li YJ; Shenzhen Bay Laboratory, Shenzhen 518055, China.
  • Wu GZ; NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
  • Quan JM; Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
  • Zhang LQ; Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center, and Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing 100084, China.
  • Tzeng YM; Department of Applied Science, Taitung University, Taitung 95092, Taiwan.
  • Yang Z; Department of Applied Chemistry, Chaoyang University of Technology, Taichung 41349, China.
Natl Sci Rev ; 9(11): nwac176, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2189437
ABSTRACT
(-)-Anisomelic acid, isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a trans-fused α-methylene-γ-lactone motif. Anisomelic acid effectively inhibits SARS-CoV-2 replication and viral-induced cytopathic effects with an EC50 of 1.1 and 4.3 µM, respectively. Challenge studies of SARS-CoV-2-infected K18-hACE2 mice showed that oral administration of anisomelic acid and subcutaneous dosing of remdesivir can both reduce the viral titers in the lung tissue at the same level. To facilitate drug discovery, we used a semisynthetic approach to shorten the project timelines. The enantioselective semisynthesis of anisomelic acid from the naturally enriched and commercially available starting material (+)-costunolide was achieved in five steps with a 27% overall yield. The developed chemistry provides opportunities for developing anisomelic-acid-based novel ligands for selectively targeting proteins involved in viral infections.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Diagnostic study Language: English Journal: Natl Sci Rev Year: 2022 Document Type: Article Affiliation country: Nsr

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Diagnostic study Language: English Journal: Natl Sci Rev Year: 2022 Document Type: Article Affiliation country: Nsr