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

Authors
  • Cao, Ruiyuan1
  • Hu, Hengrui2, 3
  • Li, Yufeng2, 3
  • Wang, Xi2
  • Xu, Mingyue2, 3
  • Liu, Jia2
  • Zhang, Huanyu2, 3
  • Yan, Yunzheng1
  • Zhao, Lei1
  • Li, Wei1
  • Zhang, Tianhong1, 4
  • Xiao, Dian1
  • Guo, Xiaojia1
  • Li, Yuexiang1
  • Yang, Jingjing1
  • Hu, Zhihong2
  • Wang, Manli2
  • Zhong, Wu1
  • 1 Beijing Institute of Pharmacology and Toxicology, China , (China)
  • 2 Chinese Academy of Sciences, P. R. China
  • 3 University of the Chinese Academy of Sciences, P. R. China
  • 4 Guoke Excellence (Beijing) Medicine Technology Research Co., Ltd., P. R. China
Type
Published Article
Journal
ACS Infectious Diseases
Publisher
American Chemical Society
Publication Date
Jul 31, 2020
Identifiers
DOI: 10.1021/acsinfecdis.0c00522
PMID: 32786284
PMCID: PMC7437450
Source
PubMed Central
Keywords
License
Green

Abstract

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.

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