- Hai-Xin Yu Peking University ,
- Nan Zheng Peking University ,
- Chi-Tai Yeh Taipei Medical University-Shuang Ho Hospital ,
- Chien-Ming Lee National Taitung University ,
- Qi Zhang Tsinghua University ,
- Wen-Lv Zheng Peking University ,
- Qing Chang Lanzhou Institute of Separation Science ,
- Yuan-He Li Peking University ,
- Gui-Zhen Wu Chinese Center For Disease Control and Prevention ,
- Jun-Min Quan Peking University ,
- Lin-Qi Zhang Tsinghua University ,
- Yew-Min Tzeng National Taitung University & Chaoyang University of Technology ,
- Zhen Yang Peking University & Shenzhen Bay Laboratory
(–)-Anisomelic acid (AA), isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a trans-fused α-methylene-β-lactone motif. Cytopathic effect assays showed that the anti-SARS-CoV-2 effect of AA (IC50 = 4.3 μM) is comparable to that of remdesivir (IC50 = 2.1 μM), and more potent than that of molnupiravir (IC50 = 27.8 μM). Challenge studies in SARS-CoV-2-infected K18-hACE2 mice showed that oral administration of AA and 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 AA 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 AA-based novel ligands for selectively targeting proteins involved in viral infection.
Added a missing reagent in the synthetic route.