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We report in vitro efficacy of <jats:italic>Artemisia annua<\/jats:italic> 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\u2013response 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<jats:sub>50<\/jats:sub>) in different cell types: 7\u201312\u00a0\u00b5g\/mL), followed by artemether (53\u201398\u00a0\u00b5g\/mL), <jats:italic>A. annua<\/jats:italic> extracts (83\u2013260\u00a0\u00b5g\/mL) and artemisinin (151 to at least 208\u00a0\u00b5g\/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<jats:sub>50<\/jats:sub> values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment.<\/jats:p>","DOI":"10.1038\/s41598-021-93361-y","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T10:03:33Z","timestamp":1626429813000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["In vitro efficacy of artemisinin-based treatments against SARS-CoV-2"],"prefix":"10.1038","volume":"11","author":[{"given":"Yuyong","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry","family":"Gilmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santseharay","family":"Ramirez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Settels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen A.","family":"Gammeltoft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long V.","family":"Pham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrik","family":"Fahn\u00f8e","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Offersgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Trimpert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Bukh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Osterrieder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith M.","family":"Gottwein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Seeberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,16]]},"reference":[{"key":"93361_CR1","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.ijid.2020.01.009","volume":"91","author":"DS Hui","year":"2020","unstructured":"Hui, D. 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