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bioRxiv · 10.1101/2020.10.23.352666

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

Le, B. L.·Andreoletti, G.·Oskotsky, T.·Vallejo-Gracia, A.·Rosales, R.·Yu, K. Z.·Kosti, I.·Leon, K. E.·Bunis, D. G.·Li, C.·Kumar, G. R.·White, K. M.·Garcia-Sastre, A. E.·Ott, M.·Sirota, M.
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Abstract

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.

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Le, B. L., Andreoletti, G., Oskotsky, T., Vallejo-Gracia, A., Rosales, R., Yu, K. Z., Kosti, I., Leon, K. E., Bunis, D. G., Li, C., Kumar, G. R., White, K. M., Garcia-Sastre, A. E., Ott, M., Sirota, M.. 2020-10-23. Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19. https://doi.org/10.1101/2020.10.23.352666

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