LAUSR

Drug repurposing is an appealing method to address the Coronavirus 2019 (COVID-19) pandemic because of their low cost and efficiency. We analyzed our in-house database of approved drug screens and compared their activity profiles with results from a severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) cytopathic effect (CPE) assay. The activity profiles of the human ether-à-go-go-related gene (hERG), phospholipidosis (PLD), and many cytotoxicity screens were significantly correlated with anti-SARS-CoV-2 activity. hERG inhibition is a nonspecific off-target effect that has contributed to promiscuous drug interactions, whereas drug-induced PLD is an undesirable effect linked to hERG blockers. Thus, this study identifies preferred drug candidates as well as chemical structures that should be avoided because of their potential to induce toxicity. Lastly, we highlight the hERG liability of anti-SARS-CoV-2 drugs currently enrolled in clinical trials. Teaser: Drug repurposing is an appealing method for the development of COVID-19 treatments; however, significant correlations observed between a SARS-CoV-2 cytopathic effect assay and hERG, phospholipidosis, and many cell viability assays raise concerns regarding the toxicity potentials of anti-SARS-CoV-2 drugs.