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

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 (+3 others)
2021 Scientific Reports  
AbstractThe 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
more » ... , 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.
doi:10.1038/s41598-021-84044-9 pmid:33627767 pmcid:PMC7904823 fatcat:u3u4hupllrallae4xm4w7twhiu