@article{90aca6c367054a67a8311656a6dc5410,
title = "Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19",
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 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.",
author = "Le, {Brian L.} and Gaia Andreoletti and Tomiko Oskotsky and Albert Vallejo-Gracia and Romel Rosales and Katharine Yu and Idit Kosti and Leon, {Kristoffer E.} and Bunis, {Daniel G.} and Christine Li and Kumar, {G. Renuka} and White, {Kris M.} and Adolfo Garc{\'i}a-Sastre and Melanie Ott and Marina Sirota",
note = "Funding Information: M.S. is on the advisory board of twoXAR. The Garc{\'i}a-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. Funding Information: This work was funded in part by the Program for Breakthrough Biomedical Research (PBBR) Grant. This research was also partly funded by the Defense Advanced Research Projects Agency (HR0011-19-2-0020); by CRIP (Center for Research for Influenza Pathogenesis), a NIAID supported Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C); by supplements to NIAID grant U19AI135972 and DoD grant W81XWH-20-1-0270; by the generous support of the JPB Foundation and the Open Philanthropy Project (research grant 2020-215611 (5384)); and by anonymous donors to A. Garc{\'i}a-Sastre. M. Ott acknowledges support through a gift from the Roddenberry Foundation and by NIH 5DP1DA038043. We would like to thank members of the Sirota Lab for useful discussion, Dr. Boris Oskotsky for technical support, Edna Rodas for administrative support, Randy Albrecht for support with the BSL3 facility and procedures at the ISMMS, and Richard Cadagan for technical assistance. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s41598-021-91625-1",
language = "English",
volume = "11",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}