| Title | Identification and semisynthesis of(-)-anisomelic acid as oral agent against SARS-CoV-2 in mice |
| Authors | 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 |
| Affiliation | Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School Department of Medicinal Research and Education,Taipei Medical University-Shuang Ho Hospital Department of Applied Science, Taitung University Center for Global Health and Infectious Diseases,Comprehensive AIDS Research Center, and Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University Lanzhou Institute of Separation Science 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 Shenzhen Bay Laboratory NHC Key Laboratory of Biosafety,National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention Department of Applied Chemistry,Chaoyang University of Technology |
| Keywords | identification enantioselective semisynthesis (-)-anisomelic acid oral agent anti-SARS-CoV-2 |
| Issue Date | 30-Nov-2022 |
| Publisher | National Science Review |
| 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-Co V-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. |
| URI | http://hdl.handle.net/20.500.11897/667348 |
| ISSN | 2095-5138 |
| Indexed | 中国科学引文数据库(CSCD) |
| Appears in Collections: | 化学生物学与生物技术学院 化学与分子工程学院 生物有机与分子工程教育部重点实验室 |
