Identification of candidate repurposable drugs to combat COVID-19 using a signature-based approach.

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.

• Authors: Sinead M O'Donovan, Ali Imami, Hunter Eby, Nicholas D Henkel, Justin Fortune Creeden, Sophie Asah, Xiaolu Zhang, Xiaojun Wu, Rawan Alnafisah, R Travis Taylor, James Reigle, Alexander Thorman, Behrouz Shamsaei, Jarek Meller, Robert E McCullumsmith
• Journal: Scientific reports (Sci Rep) Vol. 11 Issue 1 Pg. 4495 (02 24 2021) ISSN: 2045-2322 [Electronic] England
• PMID: 33627767 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antiviral Agents
• Pharmaceutical Preparations

Topics

• Antiviral Agents (pharmacology)
• COVID-19 (genetics, metabolism)
• Computational Biology (methods)
• Databases, Factual
• Drug Discovery (methods)
• Drug Repositioning (methods)
• Humans
• Pandemics
• Pharmaceutical Preparations
• SARS-CoV-2 (drug effects, genetics, metabolism)
• Transcriptome (drug effects)
• COVID-19 Drug Treatment