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

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 EC 50 of 10.28 ± 1.12 μM. Artesunate and dihydroartemisinin showed similar EC 50 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 EC 50 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.

In vitroefficacy of Artemisinin-based treatments against SARS-CoV-2

“…While compiling data for this study, Cao et al reported efficacy of artemisinin derivatives against a SARS-CoV-2 isolate from Wuhan in VeroE6 cells. 24 While extracts were not studied, the efficacy of artesunate was similar with EC50 of 13 μM compared to 18 μM in our VeroE6 treatment assay. Interestingly, EC50 for artemether and artemisinin were 8 fold and >8 fold higher in our VeroE6 treatment assay compared to values reported by Cao et al .…”

The Possible Effects of Asiatic Herbs in SARS-COV-2 and their Mechanism of Action

“…The results showed that Arteannuin B had the highest anti- respectively, which could be achieved clinically in plasma after intravenous administration. This research highlighted the anti-SARS-CoV-2 potential of artemisinins and provided the main candidates for research and development of anti-SARS-CoV2 drugs [61] .…”

“…Likewise, the use of techniques such as enveloping artemisinin in a liposome to improve bioavailability has demonstrated great efficiency in the administration of this drug [60] . compounds against COVID-19 [61] . The results showed that Arteannuin B had the highest anti- respectively, which could be achieved clinically in plasma after intravenous administration.…”

Chinese herbal medicine: Fighting SARS-CoV-2 infection on all fronts

“… No. Compound Plant EC 50 or IC 50 (μM) Reference 1 andrographolide Herba andrographitis 0.034 Sa-ngiamsuntorn et al (2020) 2 artemisinin Artemisia annua 64.45 Cao et al (2020) 3 baicalein Scutellaria baicalensis 0.39 Liu et al (2020a) 4 baicalin Scutellaria baicalensis 6.41 Su et al (2020) 5 berbamine Berberis thunbergii 7.87 Liu et al (2020a) 6 cannabidiol Cannabis sativa 7.91 Raj et al (2020) 7 cepharanthine Stephania cephalantha 0.35 Ohashi et al (2020) 8 chlorogenic acid L. japonica 39.5 Su et al (2020) 9 digitoxin Digitalis purpurea 0.23 Jeon et al (2020) 10 digoxin Digitalis purpurea 0.19 Cho et al (2020) …”

“…Based on in-depth studies, accumulating evidence has shown that artemisinin also has therapeutic efficacy for respiratory diseases ( Cheong et al, 2020 ), acute lung injury ( Zhao et al, 2017 ), myocardial ischemia-reperfusion injury ( Wang et al, 2020b ), and acute kidney injury ( Liu et al, 2019 ). Cao et al ( Cao et al, 2020 ) recently revealed that artemisinin was able to inhibit SARS-CoV-2 infection with an EC 50 value of 64.45 μM in vitro . Molecular dynamics studies also confirmed that artemisinin exhibits potent binding to Lys353 and Lys31-binding hotspots in the SARS-CoV-2 S protein ( Sehailia et al, 2020 ).…”