Department of Biological Sciences, Laboratory of Immunology and Infectious Disease Biology, Indian Institute of Science Education and Research (IISER) Bhopal, Bhopal, 462066, MP, India.
Microbiology Department, Zoram Medical College, Falkawn, Mizoram, 796005, India.
Comput Biol Med. 2021 Jan;128:104123. doi: 10.1016/j.compbiomed.2020.104123. Epub 2020 Nov 24.
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.
由冠状病毒 SARS-CoV-2 引起的持续的 COVID-19 大流行已经在全球范围内造成超过 125 万人死亡,而且这个数字还在不断增加。了解宿主对这种病毒的转录反应,以及与之前引起爆发的其他人类冠状病毒(SARS-CoV、MERS-CoV)相比,这些途径是如何被激活或抑制的,可以帮助我们确定治疗 COVID-19 的潜在药物。因此,我们使用时间点荟萃分析来研究现有的 SARS-CoV 和 MERS-CoV 体外转录组数据集,以确定在每个时间点失调的显著基因和途径。随后的过表达分析(ORA)显示,在 SARS-CoV 和 MERS-CoV 感染后,每个时间点都有几个途径明显失调。我们还对 SARS-CoV 和 MERS-CoV 与 SARS-CoV-2 进行了基因集富集分析,结果表明,所有三种冠状病毒都激活和抑制了共同的途径。此外,对 COVID-19 患者的体内转录组数据集的分析表明,富集到的途径与早期分析中确定的途径相似。基于这些发现,进行了药物再利用分析,以确定对抗 COVID-19 的潜在药物候选物。