Anti-SARS-CoV‑2 Potential of Artemisinins In Vitro

• Published in: ACS infectious diseases Vol. 6; no. 9; pp. 2524 - 2531
• Main Authors: Cao, Ruiyuan, Hu, Hengrui, Li, Yufeng, Wang, Xi, Xu, Mingyue, Liu, Jia, Zhang, Huanyu, Yan, Yunzheng, Zhao, Lei, Li, Wei, Zhang, Tianhong, Xiao, Dian, Guo, Xiaojia, Li, Yuexiang, Yang, Jingjing, Hu, Zhihong, Wang, Manli, Zhong, Wu
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 11.09.2020
• Subjects: Animals; Antimalarials - pharmacology; Antiviral Agents - pharmacology; Artemisinins - pharmacology; Betacoronavirus - drug effects; Chlorocebus aethiops; Coronavirus Infections - drug therapy; Coronavirus Infections - virology; COVID-19; Drug Discovery; Drug Repositioning; Drugs, Chinese Herbal - pharmacology; Pandemics; Pneumonia, Viral - drug therapy; Pneumonia, Viral - virology; SARS-CoV-2; Vero Cells; artemisinin; COVID-19; SARS-CoV-2; drug repurposing; antiviral drug
• ISSN: 2373-8227; 2373-8227
• DOI: 10.1021/acsinfecdis.0c00522

The discovery of novel drug candidates with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential is critical for the control of the global COVID-19 pandemic. Artemisinin, an old antimalarial drug derived from Chinese herbs, has saved millions of lives. Artemisinins are a cluster of artemisinin-related drugs developed for the treatment of malaria and have been reported to have multiple pharmacological activities, including anticancer, antiviral, and immune modulation. Considering the reported broad-spectrum antiviral potential of artemisinins, researchers are interested in whether they could be used to combat COVID-19. We systematically evaluated the anti-SARS-CoV-2 activities of nine artemisinin-related compounds in vitro and carried out a time-of-drug-addition assay to explore their antiviral mode of action. Finally, a pharmacokinetic prediction model was established to predict the therapeutic potential of selected compounds against COVID-19. Arteannuin B showed the highest anti-SARS-CoV-2 potential with an EC50 of 10.28 ± 1.12 μM. Artesunate and dihydroartemisinin showed similar EC50 values of 12.98 ± 5.30 μM and 13.31 ± 1.24 μM, respectively, which could be clinically achieved in plasma after intravenous administration. Interestingly, although an EC50 of 23.17 ± 3.22 μM was not prominent among the tested compounds, lumefantrine showed therapeutic promise due to high plasma and lung drug concentrations after multiple dosing. Further mode of action analysis revealed that arteannuin B and lumefantrine acted at the post-entry step of SARS-CoV-2 infection. This research highlights the anti-SARS-CoV-2 potential of artemisinins and provides leading candidates for anti-SARS-CoV-2 drug research and development.