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Anti-SARS-CoV-2 Potential of Artemisinins In Vitro.
ACS Infect Dis. 2020 09 11; 6(9):2524-2531.AI

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32786284

Citation

Cao, Ruiyuan, et al. "Anti-SARS-CoV-2 Potential of Artemisinins in Vitro." ACS Infectious Diseases, vol. 6, no. 9, 2020, pp. 2524-2531.
Cao R, Hu H, Li Y, et al. Anti-SARS-CoV-2 Potential of Artemisinins In Vitro. ACS Infect Dis. 2020;6(9):2524-2531.
Cao, R., Hu, H., Li, Y., Wang, X., Xu, M., Liu, J., Zhang, H., Yan, Y., Zhao, L., Li, W., Zhang, T., Xiao, D., Guo, X., Li, Y., Yang, J., Hu, Z., Wang, M., & Zhong, W. (2020). Anti-SARS-CoV-2 Potential of Artemisinins In Vitro. ACS Infectious Diseases, 6(9), 2524-2531. https://doi.org/10.1021/acsinfecdis.0c00522
Cao R, et al. Anti-SARS-CoV-2 Potential of Artemisinins in Vitro. ACS Infect Dis. 2020 09 11;6(9):2524-2531. PubMed PMID: 32786284.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-SARS-CoV-2 Potential of Artemisinins In Vitro. AU - Cao,Ruiyuan, AU - Hu,Hengrui, AU - Li,Yufeng, AU - Wang,Xi, AU - Xu,Mingyue, AU - Liu,Jia, AU - Zhang,Huanyu, AU - Yan,Yunzheng, AU - Zhao,Lei, AU - Li,Wei, AU - Zhang,Tianhong, AU - Xiao,Dian, AU - Guo,Xiaojia, AU - Li,Yuexiang, AU - Yang,Jingjing, AU - Hu,Zhihong, AU - Wang,Manli, AU - Zhong,Wu, Y1 - 2020/08/18/ PY - 2020/8/14/pubmed PY - 2020/9/24/medline PY - 2020/8/14/entrez KW - COVID-19 KW - SARS-CoV-2 KW - antiviral drug KW - artemisinin KW - drug repurposing SP - 2524 EP - 2531 JF - ACS infectious diseases JO - ACS Infect Dis VL - 6 IS - 9 N2 - 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. SN - 2373-8227 UR - https://www.unboundmedicine.com/medline/citation/32786284/Anti_SARS_CoV_2_Potential_of_Artemisinins_In_Vitro_ L2 - https://doi.org/10.1021/acsinfecdis.0c00522 DB - PRIME DP - Unbound Medicine ER -