Anti-SARS-CoV-2 Potential of Artemisinins In Vitro #MMPMID32786284
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
ACS Infect Dis 2020[Sep]; 6 (9): 2524-2531 PMID32786284show ga
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 EC(50) of 10.28 +/- 1.12 muM. Artesunate and dihydroartemisinin showed similar EC(50) values of 12.98 +/- 5.30 muM and 13.31 +/- 1.24 muM, respectively, which could be clinically achieved in plasma after intravenous administration. Interestingly, although an EC(50) of 23.17 +/- 3.22 muM 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.
ACS+Infect+Dis 2020 ; 6 (9): 2524-2531
