In vitro efficacy of artemisinin-based treatments against SARS-CoV-2

• Published in: Scientific reports Vol. 11; no. 1; p. 14571
• Main Authors: Zhou, Yuyong, Gilmore, Kerry, Ramirez, Santseharay, Settels, Eva, Gammeltoft, Karen A., Pham, Long V., Fahnøe, Ulrik, Feng, Shan, Offersgaard, Anna, Trimpert, Jakob, Bukh, Jens, Osterrieder, Klaus, Gottwein, Judith M., Seeberger, Peter H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.07.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/154; 692/699/255/2514; Antiviral agents; Artemether; Artemisia annua; Artemisinin; Artesunate; Cell viability; Coronaviruses; COVID-19; Hepatoma; Humanities and Social Sciences; Lung cancer; multidisciplinary; Plant extracts; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Spike glycoprotein
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-93361-y

Effective and affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are needed. We report in vitro efficacy of Artemisia annua extracts as well as artemisinin, artesunate, and artemether against SARS-CoV-2. The latter two are approved active pharmaceutical ingredients of anti-malarial drugs. Concentration–response antiviral treatment assays, based on immunostaining of SARS-CoV-2 spike glycoprotein, revealed that treatment with all studied extracts and compounds inhibited SARS-CoV-2 infection of VeroE6 cells, human hepatoma Huh7.5 cells and human lung cancer A549-hACE2 cells, without obvious influence of the cell type on antiviral efficacy. In treatment assays, artesunate proved most potent (range of 50% effective concentrations (EC 50 ) in different cell types: 7–12 µg/mL), followed by artemether (53–98 µg/mL), A. annua extracts (83–260 µg/mL) and artemisinin (151 to at least 208 µg/mL). The selectivity indices (SI), calculated based on treatment and cell viability assays, were mostly below 10 (range 2 to 54), suggesting a small therapeutic window. Time-of-addition experiments in A549-hACE2 cells revealed that artesunate targeted SARS-CoV-2 at the post-entry level. Peak plasma concentrations of artesunate exceeding EC 50 values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment.