Abstract
Although extrapulmonary manifestations of coronavirus disease 2019 (COVID-19) are increasingly reported, no effective therapeutic strategy for these multisystemic complications is available due to a poor understanding of the pathophysiology of COVID-19 multiorgan involvement. In this study, differentially expressed genes (DEGs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected extrapulmonary organs including human pluripotent stem cells (hPSCs)-derived liver organoids and choroid plexus organoids besides transformed lung alveolar (A549) cells were analyzed. First, pathway enrichment analysis was done to compare the underlying biological pathways enriched upon SARS-CoV-2 infection in different organs. Then, these lists of DEGs were used in a connectivity map (CMap)-based drug repurposing experiment. Also, protein-protein interaction (PPI) network analysis was done to compare the associated hub genes. The results revealed different biological pathways and genes responsible for SARS-CoV-2 multisystemic pathogenesis based on the organ involved that highlighted the need for considering organ-specific treatments or even personalized therapy. Besides, some FDA-approved drugs were proposed as the potential therapeutic candidates for each infected cell line.
Keywords: COVID-19; SARS-CoV-2; Organ-specific treatment; Personalized medicine; Drug repurposing.
【저자키워드】 COVID-19, SARS-CoV-2, drug repurposing., Personalized medicine, Organ-specific treatment, 【초록키워드】 Treatment, coronavirus disease, Drug repurposing, coronavirus, therapy, Pathogenesis, SARS-COV-2 infection, pathophysiology, therapeutic, Complication, network analysis, experiment, liver, protein-protein interaction, therapeutic strategy, differentially expressed gene, Multiorgan, A549, PPI, Pathway enrichment analysis, Organoid, manifestation, acute respiratory syndrome, FDA-approved drug, candidate, multisystemic, organs, DEGs, infected cell, organ, Genes, pluripotent stem cell, effective, Cell, responsible, analyzed, involved, reported, were used, increasingly, was done, biological pathway, extrapulmonary organ, lung alveolar, organ-specific, 【제목키워드】 Treatment, Evidence, candidate,