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Sci Rep
. 2021 Feb 24;11(1):4495.
doi: 10.1038/s41598-021-84044-9.
Identification of candidate repurposable drugs to combat COVID-19 using a signature-based approach
Sinead M O'Donovan # 1 , Ali Imami # 1 , Hunter Eby 1 , Nicholas D Henkel 1 , Justin Fortune Creeden 1 , Sophie Asah 1 , Xiaolu Zhang 1 , Xiaojun Wu 1 , Rawan Alnafisah 1 , R Travis Taylor 2 , James Reigle 3 4 , Alexander Thorman 5 , Behrouz Shamsaei 4 , Jarek Meller 4 6 5 7 8 , Robert E McCullumsmith 9 10
Affiliations
- PMID: 33627767
- DOI: 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.