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

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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 (EC50) 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 EC50 values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment.

OriginalsprogEngelsk
Artikelnummer14571
TidsskriftScientific Reports
Vol/bind11
ISSN2045-2322
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
We thank the Max Planck Society for financial support. This work was supported by a PhD stipend from the China Scholarship Council (Y.Z.) and a grant from the Danish Agency for Science and Higher Education (J.B.). We thank Dr. Bjarne Ø. Lindhardt (Copenhagen University Hospital-Hvidovre) and Prof. Carsten Geisler (University of Copenhagen) for support from Hvidovre Hospital and the University of Copenhagen. We thank Lotte Mikkelsen, Anna-Louise Sørensen, and Pia Pedersen (Copenhagen University Hospital-Hvidovre) for laboratory assistance. We thank Dr. Christoph Rademacher and Felix Fuchsberger for helpful conversations. We thank ArtemiLife Inc. for providing the A. annua plant material. We thank Prof. Jean Dubuisson and Dr. Sandrine Belouzard for providing VeroE6 cells. We thank Dr. Daniela Niemeyer and Prof. Christian Drosten for providing the SARS-CoV-2/human/Germany/BavPat 1/2020 isolate.

Publisher Copyright:
© 2021, The Author(s).

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