Identification and semisynthesis of(-)-anisomelic acid as oral agent against SARS-CoV-2 in mice  

作　　者：Hai-Xin Yu Nan Zheng Chi-Tai Yeh Chien-Ming Lee Qi Zhang Wen-Lv Zheng Qing Chang Yuan-He Li Yu-Jun Li Gui-Zhen Wu Jun-Min Quan Lin-Qi Zhang Yew-Min Tzeng Zhen Yang 

机构地区：[1]Laboratory of Chemical Genomics,School of Chemical Biology and Biotechnology,Peking University Shenzhen Graduate School,Shenzhen 518055 [2]Department of Medicinal Research and Education,Taipei Medical University-Shuang Ho Hospital,New Taipei City 23561 [3]Department of Applied Science,Taitung University,Taitung 95092 [4]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 [5]Lanzhou Institute of Separation Science,Lanzhou 730013 [6]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 [7]Shenzhen Bay Laboratory,Shenzhen 518055 [8]NHC Key Laboratory of Biosafety,National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206 [9]Department of Applied Chemistry,Chaoyang University of Technology,Taichung 41349

出　　处：《National Science Review》2022年第11期24-31,共8页国家科学评论（英文版）

基　　金：supported by the National Natural Science Foundation of China (21772004, 21871012, 21933004, 21632002,21521003 and 22077009);the Ministry of Science and Technology of China (2022YFC0868400)

摘　　要：(-)-Anisomelic acid,isolated from Anisomeles indica(L.)Kuntze(Labiatae)leaves,is a macrocyclic cembranolide with a trans-fusedα-methylene-γ-lactone motif.Anisomelic acid effectively inhibits SARS-Co V-2 replication and viral-induced cytopathic effects with an EC50 of 1.1 and 4.3μM,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.

关 键 词：IDENTIFICATION enantioselective semisynthesis (-)-anisomelic acid oral agent anti-SARS-CoV-2 

分 类 号：R965[医药卫生—药理学]