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.
【저자키워드】 viral infection, Drug discovery, 【초록키워드】 COVID-19, Treatment, coronavirus disease, SARS-CoV-2, Efficacy, coronavirus, SARS-COV-2 infection, Cancer, Antiviral treatment, in vitro, Artemisinin, cells, viability, SARS-CoV-2 spike glycoprotein, clinical, human lung, Patient, antiviral efficacy, ingredient, experiment, utility, immunostaining, therapeutic window, plasma concentration, acute respiratory syndrome, Anti-malarial drugs, Compound, VeroE6 cells, hepatoma, 50% effective concentration, peak, Cell, evaluate, caused, assays, required, inhibited, approved, calculated, these compound, Huh7.5 cell, 【제목키워드】 Treatment, SARS-CoV-2, Efficacy,