A negative connectivity score shows that the compound can reverse the genomic signature of the disease so, it can be proposed as the therapeutic option for the mentioned disease (Qu and Rajpal 2012). Results of the CMap analysis would be shown with a connectivity score for each drug-disease pair ranging from − 1 to + 1.
Transcriptomic signatures of SARS-CoV-2-infected cells were compared with genomic signatures of cell lines treated with various compounds known as connectivity map (CMap). Besides, we set out to perform a drug repurposing experiment. Since infectious microorganisms such as the SARS-CoV-2 virus change the host transcriptome and gene expression of the infected cells in the way optimal for their replication, gene expression analysis can help to understand the underlying mechanisms involved in SARS-CoV-2 pathogenesis and host immune system dysregulation through COVID-19. Since available experiments analyzing SARS-CoV-2-infected extrapulmonary tissues are scant, we aimed to analyze transcriptomic signatures of SARS-CoV-2-infected cell lines belonging to different organs to compare the genes and their associated functional pathways responsible for viral pathogenesis in each organ. However, the mechanism of SARS-CoV-2 multiorgan involvement is still unknown. Although initial studies showed COVID-19 as a respiratory tract infection, recent investigations have revealed the multisystemic nature of this virus. Besides, some FDA-approved drugs were proposed as the potential therapeutic candidates for each infected cell line.Ĭoronavirus disease 2019 (COVID-19) was first reported in China rapidly spreading across the world. 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. Also, protein–protein interaction (PPI) network analysis was done to compare the associated hub genes. Then, these lists of DEGs were used in a connectivity map (CMap)-based drug repurposing experiment. First, pathway enrichment analysis was done to compare the underlying biological pathways enriched upon SARS-CoV-2 infection in different organs. 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.
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.
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