Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs. We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients. We found 581 significantly correlated interactions, between 95 TFs and 16 cytokines upregulated in the COVID-19 patients, that may contribute to pathogenesis of the disease. Among these, we identified 19 TFs that are targets of FDA approved drugs. We investigated the potential therapeutic effect of 10 drugs and 25 drugs combinations on inflammatory cytokine production, which revealed two drugs that inhibited cytokine production and numerous combinations that show synergistic efficacy in downregulating cytokine production. Further studies of these candidate repurposable drugs could lead to a therapeutic regimen to treat the CRS in COVID-19 patients.
【저자키워드】 COVID-19, Drug repurposing, Cytokine storm, SARS-CoV2, Gene regulatory networks, Cytokine release syndrome, transcriptional regulators, 【초록키워드】 Efficacy, Pathogenesis, TFS, cytokine, drug, approved drugs, Bronchoalveolar lavage fluid, single-cell RNA-seq, therapeutic, target, resource, interactions, cytokine production, Inflammatory cytokine, COVID-19 patients, CRS, Combination, FDA approved Drugs, Interaction, therapeutic targeting, regimen, transcription factor, hospitalized COVID-19 patients, therapeutic effect, treat, expression data, transcriptional regulator, inflammatory cytokine production, Cell, synergistic, identify, significantly, involved, investigated, the disease, inhibited, contribute, correlated, upregulated, downregulating, 【제목키워드】 Release, Control, Factor, targeting,