Identification of candidate repurposable drugs to combat COVID-19 using a signature-based approach
Open Access
- 24 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 11 (1), 1-12
- https://doi.org/10.1038/s41598-021-84044-9
Abstract
The COVID-19 pandemic caused by the novel SARS-CoV-2 is more contagious than other coronaviruses and has higher rates of mortality than influenza. Identification of effective therapeutics is a crucial tool to treat those infected with SARS-CoV-2 and limit the spread of this novel disease globally. We deployed a bioinformatics workflow to identify candidate drugs for the treatment of COVID-19. Using an "omics" repository, the Library of Integrated Network-Based Cellular Signatures (LINCS), we simultaneously probed transcriptomic signatures of putative COVID-19 drugs and publicly available SARS-CoV-2 infected cell lines to identify novel therapeutics. We identified a shortlist of 20 candidate drugs: 8 are already under trial for the treatment of COVID-19, the remaining 12 have antiviral properties and 6 have antiviral efficacy against coronaviruses specifically, in vitro. All candidate drugs are either FDA approved or are under investigation. Our candidate drug findings are discordant with (i.e., reverse) SARS-CoV-2 transcriptome signatures generated in vitro, and a subset are also identified in transcriptome signatures generated from COVID-19 patient samples, like the MEK inhibitor selumetinib. Overall, our findings provide additional support for drugs that are already being explored as therapeutic agents for the treatment of COVID-19 and identify promising novel targets that are worthy of further investigation.Funding Information
- National Institute of Mental Health (MH107487)
- National Institute on Aging (AG057598)
This publication has 103 references indexed in Scilit:
- Fold change rank ordering statistics: a new method for detecting differentially expressed genesBMC Bioinformatics, 2014
- Inhibitors of Alphavirus Entry and Replication Identified with a Stable Chikungunya Replicon Cell Line and Virus-Based AssaysPLOS ONE, 2011
- Rift Valley Fever Virus Infection of Human Cells and Insect Hosts Is Promoted by Protein Kinase C EpsilonPLOS ONE, 2010
- Inhibition of Encephalomyocarditis Virus and Poliovirus Replication by Quinacrine: Implications for the Design and Discovery of Novel Antiviral DrugsJournal of Virology, 2010
- Reproducibility of microarray data: a further analysis of microarray quality control (MAQC) dataBMC Bioinformatics, 2007
- Inhibition of HIV-1 replication by P-TEFb inhibitors DRB, seliciclib and flavopiridol correlates with release of free P-TEFb from the large, inactive form of the complexRetrovirology, 2007
- Random-set methods identify distinct aspects of the enrichment signal in gene-set analysisThe Annals of Applied Statistics, 2007
- Suppression of Coronavirus Replication by Inhibition of the MEK Signaling PathwayJournal of Virology, 2007
- Cross-platform comparability of microarray technology: Intra-platform consistency and appropriate data analysis procedures are essentialBMC Bioinformatics, 2005
- Gene Expression Omnibus: NCBI gene expression and hybridization array data repositoryNucleic Acids Research, 2002