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.
【저자키워드】 Drug discovery, Computational biology and bioinformatics, 【초록키워드】 COVID-19, Treatment, SARS-CoV-2, SARS-CoV-2 virus, drug, antiviral activity, validation, Antiviral assays, experiment, Differentially expressed genes, Calu-3, differentially expressed gene, human cell lines, Differential gene expression, antiviral assay, Analysis, haloperidol, Clofazimine, treatment of COVID-19, available data, profile, Compound, novel SARS-CoV-2 virus, live SARS-CoV-2, 293T, 293T-ACE2 cells, Calu, Computational drug, connectivity, statistic, effective, independent, initial, tested, predicted, generate, applied, Map, human cell line, 【제목키워드】 COVID-19, therapeutic, candidate, identify,