Abstract
Drug repurposing is an appealing method to address the Coronavirus 2019 (COVID-19) pandemic because of the 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 found 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.
Keywords: Autophagy; COVID-19; Cytotoxicity; Drug repurposing; High-throughput screening; In vitro assay; Phospholipidosis; SARS-CoV-2; hERG.
【저자키워드】 COVID-19, Drug repurposing, SARS-CoV-2, cytotoxicity, High-throughput screening, autophagy, In vitro assay, Phospholipidosis, hERG., 【초록키워드】 Drug repurposing, Structure, pandemic, clinical trials, Toxicity, cytotoxicity, drug, anti-SARS-CoV-2, database, autophagy, Severe acute respiratory syndrome, CPE, Phospholipidosis, Cytopathic effect, Drug interactions, Anti-SARS-CoV-2 Activity, Efficiency, chemical structures, profile, house, drug candidates, drug candidate, blockers, hERG, highlight, ether, enrolled, analyzed, identify, significantly, approved, correlated, induce, contributed, nonspecific, 【제목키워드】 repurposing, drug,