1. Academic Validation
  2. Anti-SARS-CoV-2 Potential of Artemisinins In Vitro

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

  • ACS Infect Dis. 2020 Sep 11;6(9):2524-2531. doi: 10.1021/acsinfecdis.0c00522.
Ruiyuan Cao 1 Hengrui Hu 2 3 Yufeng Li 2 3 Xi Wang 2 Mingyue Xu 2 3 Jia Liu 2 Huanyu Zhang 2 3 Yunzheng Yan 1 Lei Zhao 1 Wei Li 1 Tianhong Zhang 1 4 Dian Xiao 1 Xiaojia Guo 1 Yuexiang Li 1 Jingjing Yang 1 Zhihong Hu 2 Manli Wang 2 Wu Zhong 1
Affiliations

Affiliations

  • 1 National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • 2 State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, P. R. China.
  • 3 University of the Chinese Academy of Sciences, Beijing 100049, P. R. China.
  • 4 Guoke Excellence (Beijing) Medicine Technology Research Co., Ltd., Beijing 100176, P. R. China.
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.

Keywords

COVID-19; SARS-CoV-2; antiviral drug; artemisinin; drug repurposing.

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