Identifying potential novel insights for COVID-19 pathogenesis and therapeutics using an integrated bioinformatics analysis of host transcriptome

Abstract The molecular mechanisms underlying the pathogenesis of COVID-19 has not been fully discovered. This study aims to decipher potentially hidden parts of the pathogenesis of COVID-19, potential novel drug targets, and to identify potential drug candidates. Two gene expression profiles (GSE147507-GSE153970) were analyzed and overlapping differentially expressed genes (DEGs) were selected for which top enriched transcription factors and kinases were identified and pathway analysis was performed. Protein-protein interaction (PPI) of DEGs was constructed, hub genes were identified and module analysis was also performed. DGIdb database was used to identify drugs for the potential targets (hub genes and the most enriched transcription factors and kinases for DEGs). A drug-potential target network was constructed and drugs are ranked according to the degree. L1000FDW web-based utility was used to identify drugs that can reverse transcriptional profiles of COVID-19. We identified drugs currently in clinical trials and novel potential 8 drugs. Besides the well-known pathogenic pathways, It was found that axon guidance is a potential pathogenic pathway. Sema7A, which may exacerbate hypercytokinemia, is considered a potential novel drug target. Another potential novel pathway is related to TINF2 overexpression which may induce potential telomere dysfunction and hence DNA damage that may exacerbate lung fibrosis.