학술논문

Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19.
Document Type
article
Source
Scientific reports. 11(1)
Subject
Humans
Antiviral Agents
Computational Biology
Drug Repositioning
Transcriptome
COVID-19
SARS-CoV-2
Vaccine Related
Infectious Diseases
Biodefense
Pneumonia
Emerging Infectious Diseases
Lung
Prevention
5.1 Pharmaceuticals
Infection
Language
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.