The ongoing COVID-19 pandemic caused by the coronavirus, SARS-CoV-2, has already caused in excess of 1.25 million deaths worldwide, and the number is increasing. Knowledge of the host transcriptional response against this virus and how the pathways are activated or suppressed compared to other human coronaviruses (SARS-CoV, MERS-CoV) that caused outbreaks previously can help in the identification of potential drugs for the treatment of COVID-19. Hence, we used time point meta-analysis to investigate available SARS-CoV and MERS-CoV in-vitro transcriptome datasets in order to identify the significant genes and pathways that are dysregulated at each time point. The subsequent over-representation analysis (ORA) revealed that several pathways are significantly dysregulated at each time point after both SARS-CoV and MERS-CoV infection. We also performed gene set enrichment analyses of SARS-CoV and MERS-CoV with that of SARS-CoV-2 at the same time point and cell line, the results of which revealed that common pathways are activated and suppressed in all three coronaviruses. Furthermore, an analysis of an in-vivo transcriptomic dataset of COVID-19 patients showed that similar pathways are enriched to those identified in the earlier analyses. Based on these findings, a drug repurposing analysis was performed to identify potential drug candidates for combating COVID-19. Graphical abstract Image 1 Highlights • SARS-CoV-2 mostly alters the host pathways similar to SARS-CoV and MERS-CoV. • Many innate immune pathways were activated upon all three H-CoVs infection in-vitro. • Glutathione metabolism and mitochondrial pathways were suppressed upon infection in-vitro. • COVID-19 patients show altered ribosomes and mitochondrial pathways. • Drug repositioning analysis identified potential drug candidates against COVID-19.
【저자키워드】 Meta-analysis, Transcriptome, Drug repurposing, SARS-CoV-2, coronavirus, COVID-19, coronavirus disease-2019, SARS-COV-2, severe acute respiratory syndrome coronavirus-2, drug candidates, MERS-CoV, Middle East respiratory syndrome, SARS-CoV, severe acute respiratory syndrome,