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

• Published in: Scientific reports Vol. 11; no. 1; pp. 12310 - 14
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.06.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114; 631/154; ACE2; Angiotensin-converting enzyme 2; Antiviral activity; Antiviral agents; Antiviral Agents - pharmacology; Cell lines; Clofazimine; Computational Biology - methods; Computer applications; Coronaviruses; COVID-19; COVID-19 - genetics; COVID-19 Drug Treatment; Drug Repositioning - methods; Gene expression; Haloperidol; Humanities and Social Sciences; Humans; multidisciplinary; SARS-CoV-2 - drug effects; SARS-CoV-2 - physiology; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Transcriptome - drug effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-91625-1

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 16 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.