Integrative Transcriptome Analyses Empower the Anti-COVID-19 Drug Arsenal

The beginning of the 21st century has been marked by three distinct waves of zoonotic coronavirus outbreaks into the human population. The COVID-19 (coronavirus disease 2019) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and emerged as a global threat endangering the livelihoods of millions worldwide. Currently, and despite collaborative efforts, diverse therapeutic strategies from ongoing clinical trials are still debated. To address the need for such an immediate call of action, we leveraged the largest dataset of drug-induced transcriptomic perturbations, public SARS-CoV-2 transcriptomic datasets, and expression profiles from normal lung transcriptomes. Most importantly, our unbiased systems biology approach prioritized more than 50 repurposable drug candidates (e.g., corticosteroids, Janus kinase and Bruton kinase inhibitors). Further clinical investigation of these FDA-approved candidates as monotherapy or in combination with an antiviral regimen (e.g., remdesivir) could lead to promising outcomes in patients with COVID-19. [Display omitted] •A large repertoire of drug repurposing across SARS-CoV-2 transcriptomic settings•Pathway enrichment revealed TNF-NF-κB signaling as a targetable hallmark for COVID-19•Drug enrichment identified BTK inhibitors as repurposable candidates for COVID-19•Identified drug candidates warrant investigation in models of SARS-CoV-2 infection Virology; Bioinformatics; Systems Biology