biostudies-literatureYu HXMinistry of Science and TechnologyNational Natural Science Foundation of Chinanwac176https://www.ebi.ac.uk/biostudies/studies/S-EPMC9798891biostudies-literatureUnknown9(11)(-)-Anisomelic acid, isolated from <i>Anisomeles indica</i> (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a <i>trans</i>-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 iNational science reviewIdentification and semisynthesis of (-)-anisomelic acid as oral agent against SARS-CoV-2 in mice.PMC97988912207700921772004218710122022YFC0868400215210032163200221933004Chang QWu GZYeh CTLi YJZhang LQZheng WLLi YHTzeng YMZhang QYu HXYang ZLee CMZheng NQuan JMfalseIdentification and semisynthesis of (-)-anisomelic acid as oral agent against SARS-CoV-2 in mice.(-)-Anisomelic acid, isolated from <i>Anisomeles indica</i> (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a <i>trans</i>-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 i2022-01-01T00:00:00Z2022 Nov2025-04-18T13:20:48.29Z2024-11-14T07:59:08.021ZS-EPMC97988913660113810.1093/nsr/nwac176