Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19

Le, Brian L.; Andreoletti, Gaia; Oskotsky, Tomiko; Vallejo-Gracia, Albert; Rosales, Romel; Yu, Katharine; Kosti, Idit; Leon, Kristoffer E.; Bunis, Daniel G.; Li, Christine; Kumar, G. Renuka; White, Kris M.; García-Sastre, Adolfo; Ott, Melanie; Sirota, Marina

The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available data. We utilized three independent published studies to acquire or generate lists of differentially expressed genes between control and SARS-CoV-2-infected samples. Using a rank-based pattern matching strategy based on the Kolmogorov-Smirnov Statistic, the signatures were queried against drug profiles from Connectivity Map (CMap). We validated sixteen of our top predicted hits in live SARS-CoV-2 antiviral assays in either Calu-3 or 293T-ACE2 cells. Validation experiments in human cell lines showed that 11 of the 16 compounds tested to date (including clofazimine, haloperidol and others) had measurable antiviral activity against SARS-CoV-2. These initial results are encouraging as we continue to work towards a further analysis of these predicted drugs as potential therapeutics for the treatment of COVID-19.