RT Journal Article
SR Electronic
T1 Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.23.352666
DO 10.1101/2020.10.23.352666
A1 Brian L. Le
A1 Gaia Andreoletti
A1 Tomiko Oskotsky
A1 Albert Vallejo-Gracia
A1 Romel Rosales
A1 Katharine Yu
A1 Idit Kosti
A1 Kristoffer E. Leon
A1 Daniel G. Bunis
A1 Christine Li
A1 G. Renuka Kumar
A1 Kris M. White
A1 Adolfo García-Sastre
A1 Melanie Ott
A1 Marina Sirota
YR 2020
UL http://biorxiv.org/content/early/2020/10/23/2020.10.23.352666.abstract
AB 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.Competing Interest StatementM.S. is on the advisory board of twoXAR. The García-Sastre Laboratory has received research support from Pfizer, Senhwa Biosciences and 7Hills Pharma. A.G.S. has consulting agreements for the following companies involving cash and/or stock: Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Vaxalto, Accurius and Esperovax. Other authors declare no competing financial interests.