Lessons Learned From Limited Overlap of 15 In Vitro COVID-19 Drug Repurposing Screens

Drug repurposing can quickly and cost-effectively identify medical countermeasures against pathogens with pandemic potential and could be used as a down-selection method for selecting US Food and Drug Administration-approved drugs to test in clinical trials. We compared results from 15 high-throughput in vitro screening efforts that tested approved and clinically evaluated drugs for activity against SARS-CoV-2 replication. From the 15 studies, 304 drugs were identified as displaying the highest level of confidence from the individual screens. Of those 304 drugs, 30 were identified in 2 or more screens, while only 3 drugs (apilimod, tetrandrine, and salinomycin) were identified in 4 screens. The lack of concordance in high-confidence hits and variations in protocols makes it challenging to use the collective data as down-selection criteria for identifying repurposing candidates to move into a clinical trial.