tetano
Editor, Senior Moderator
Sci Rep
. 2021 Jul 16;11(1):14571.
doi: 10.1038/s41598-021-93361-y.
In vitro efficacy of artemisinin-based treatments against SARS-CoV-2
Yuyong Zhou[SUP] #[/SUP][SUP] 1 2 [/SUP], Kerry Gilmore[SUP] #[/SUP][SUP] 3 [/SUP], Santseharay Ramirez[SUP] 1 2 [/SUP], Eva Settels[SUP] 3 [/SUP], Karen A Gammeltoft[SUP] 1 2 [/SUP], Long V Pham[SUP] 1 2 [/SUP], Ulrik Fahnøe[SUP] 1 2 [/SUP], Shan Feng[SUP] 1 2 [/SUP], Anna Offersgaard[SUP] 1 2 [/SUP], Jakob Trimpert[SUP] 4 [/SUP], Jens Bukh[SUP] 1 2 [/SUP], Klaus Osterrieder[SUP] 5 6 [/SUP], Judith M Gottwein[SUP] 7 8 [/SUP], Peter H Seeberger[SUP] 9 10 [/SUP]
Affiliations
Abstract
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[SUB]50[/SUB]) 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[SUB]50[/SUB] values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment.
. 2021 Jul 16;11(1):14571.
doi: 10.1038/s41598-021-93361-y.
In vitro efficacy of artemisinin-based treatments against SARS-CoV-2
Yuyong Zhou[SUP] #[/SUP][SUP] 1 2 [/SUP], Kerry Gilmore[SUP] #[/SUP][SUP] 3 [/SUP], Santseharay Ramirez[SUP] 1 2 [/SUP], Eva Settels[SUP] 3 [/SUP], Karen A Gammeltoft[SUP] 1 2 [/SUP], Long V Pham[SUP] 1 2 [/SUP], Ulrik Fahnøe[SUP] 1 2 [/SUP], Shan Feng[SUP] 1 2 [/SUP], Anna Offersgaard[SUP] 1 2 [/SUP], Jakob Trimpert[SUP] 4 [/SUP], Jens Bukh[SUP] 1 2 [/SUP], Klaus Osterrieder[SUP] 5 6 [/SUP], Judith M Gottwein[SUP] 7 8 [/SUP], Peter H Seeberger[SUP] 9 10 [/SUP]
Affiliations
- PMID: 34272426
- DOI: 10.1038/s41598-021-93361-y
Abstract
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[SUB]50[/SUB]) 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[SUB]50[/SUB] values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment.