Drug Repurposing Screen for Compounds Inhibiting the Cytopathic Effect of SARS-CoV-2

• Published in: Frontiers in pharmacology Vol. 11; p. 592737
• Main Authors: Chen, Catherine Z, Shinn, Paul, Itkin, Zina, Eastman, Richard T, Bostwick, Robert, Rasmussen, Lynn, Huang, Ruili, Shen, Min, Hu, Xin, Wilson, Kelli M, Brooks, Brianna M, Guo, Hui, Zhao, Tongan, Klump-Thomas, Carleen, Simeonov, Anton, Michael, Samuel G, Lo, Donald C, Hall, Matthew D, Zheng, Wei
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 25.01.2021
• Subjects: COVID-19; cytopathic effect; drug repurposing and discovery; HTS; Pharmacology; SARS-CoV-2; COVID-19; SARS-CoV-2; drug repurposing and discovery; HTS; cytopathic effect
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2020.592737

Drug repurposing is a rapid approach to identify therapeutics for the treatment of emerging infectious diseases such as COVID-19. To address the urgent need for treatment options, we carried out a quantitative high-throughput screen using a SARS-CoV-2 cytopathic assay with a compound collection of 8,810 approved and investigational drugs, mechanism-based bioactive compounds, and natural products. Three hundred and nineteen compounds with anti-SARS-CoV-2 activities were identified and confirmed, including 91 approved drugs and 49 investigational drugs. The anti-SARS-CoV-2 activities of 230 of these confirmed compounds, of which 38 are approved drugs, have not been previously reported. Chlorprothixene, methotrimeprazine, and piperacetazine were the three most potent FDA-approved drugs with anti-SARS-CoV-2 activities. These three compounds have not been previously reported to have anti-SARS-CoV-2 activities, although their antiviral activities against SARS-CoV and Ebola virus have been reported. These results demonstrate that this comprehensive data set is a useful resource for drug repurposing efforts, including design of new drug combinations for clinical trials for SARS-CoV-2.