TY - JOUR T1 - <em>In vitro</em> efficacy of Artemisinin-based treatments against SARS-CoV-2 JF - bioRxiv DO - 10.1101/2020.10.05.326637 SP - 2020.10.05.326637 AU - Kerry Gilmore AU - Yuyong Zhou AU - Santseharay Ramirez AU - Long V. Pham AU - Ulrik Fahnøe AU - Shan Feng AU - Anna Offersgaard AU - Jakob Trimpert AU - Jens Bukh AU - Klaus Osterrieder AU - Judith M. Gottwein AU - Peter H. Seeberger Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/10/05/2020.10.05.326637.abstract N2 - 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.Proof-of-concept for prophylactic efficacy of the extracts was obtained using a plaque-reduction assay in VeroE6 cells. Subsequent concentration-response studies using a high-throughput antiviral assay, based on immunostaining of SARS-CoV-2 spike glycoprotein, revealed that pretreatment and treatment with extracts, artemisinin, and artesunate inhibited SARS-CoV-2 infection of VeroE6 cells. In treatment assays, artesunate (50% effective concentration (EC50): 7 μg/mL) was more potent than the tested plant extracts (128-260 μg/mL) or artemisinin (151 μg/mL) and artemether (&gt;179 μg/mL), while generally EC50 in pretreatment assays were slightly higher. The selectivity index (SI), calculated based on treatment and cell viability assays, was highest for artemisinin (54), and roughly equal for the extracts (5-10), artesunate (6) and artemether (&lt;7). Similar results were obtained in human hepatoma Huh7.5 cells. Peak plasma concentrations of artesunate exceeding EC50 values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment.Competing Interest StatementK.G. is the director of ArtemiLife, Inc. K.G. and P.H.S. have a significant financial stake in ArtemiFlow GmbH, that is a shareholder in ArtemiLife, Inc.List of abbreviations(API)Active pharmaceutical ingredients(CC50)median cytotoxic concentration(COVID-19)coronavirus disease 2019(DMSO)dimethylsulfoxide(EC50)median effective concentration(FBS)fetal bovine serum(FDA)Food and Drug Administration(IF)immunofluorescence(PBS)phosphate buffered saline(SD)standard deviation(SEM)standard error of the mean(SI)selectivity index(SARS-CoV-2)severe acute respiratory syndrome coronavirus 2 ER -