Department of Genome Mapping, Molecular Genetics and Genome Mapping Laboratory, Agricultural Genetic Engineering Research Institute, Giza, Egypt.
Department of Biomedical Sciences College of Health Sciences, QU Health, Qatar University, Doha, Qatar.
PLoS One. 2020 Dec 10;15(12):e0243270. doi: 10.1371/journal.pone.0243270. eCollection 2020.
The SARS-CoV-2 (COVID-19) pandemic is a global crisis that threatens our way of life. As of November 18, 2020, SARS-CoV-2 has claimed more than 1,342,709 lives, with a global mortality rate of ~2.4% and a recovery rate of ~69.6%. Understanding the interaction of cellular targets with the SARS-CoV-2 infection is crucial for therapeutic development. Therefore, the aim of this study was to perform a comparative analysis of transcriptomic signatures of infection of SARS-CoV-2 compared to other respiratory viruses (EBOV, H1N1, MERS-CoV, and SARS-CoV), to determine a unique anti-SARS-CoV-2 gene signature. We identified for the first time that molecular pathways for heparin-binding, RAGE, miRNA, and PLA2 inhibitors were associated with SARS-CoV-2 infection. The NRCAM and SAA2 genes, which are involved in severe inflammatory responses, and the FGF1 and FOXO1 genes, which are associated with immune regulation, were found to be associated with the cellular gene response to SARS-CoV-2 infection. Moreover, several cytokines, most significantly IL-8 and IL-6, demonstrated key associations with SARS-CoV-2 infection. Interestingly, the only response gene that was shared among the five viral infections was SERPINB1. The protein-protein interaction (PPI) analysis shed light on genes with high interaction activity that SARS-CoV-2 shares with other viral infections. The findings showed that the genetic pathways associated with rheumatoid arthritis, the AGE-RAGE signaling system, malaria, hepatitis B, and influenza A were of high significance. We found that the virogenomic transcriptome of infection, gene modulation of host antiviral responses, and GO terms of SARS-CoV-2 and EBOV were more similar than to SARS, H1N1, and MERS. This work compares the virogenomic signatures of highly pathogenic viruses and provides valid targets for potential therapy against SARS-CoV-2.
SARS-CoV-2（COVID-19）大流行是一场全球性危机，威胁着我们的生活方式。截至 2020 年 11 月 18 日，SARS-CoV-2 已导致超过 1,342,709 人死亡，全球死亡率约为 2.4%，康复率约为 69.6%。了解细胞靶标与 SARS-CoV-2 感染的相互作用对于治疗开发至关重要。因此，本研究旨在对 SARS-CoV-2 与其他呼吸道病毒（EBOV、H1N1、MERS-CoV 和 SARS-CoV）的感染转录组特征进行比较分析，以确定独特的抗 SARS-CoV-2 基因特征。我们首次发现，肝素结合、RAGE、miRNA 和 PLA2 抑制剂的分子途径与 SARS-CoV-2 感染有关。参与严重炎症反应的 NRCAM 和 SAA2 基因，以及与免疫调节相关的 FGF1 和 FOXO1 基因，与 SARS-CoV-2 感染的细胞基因反应有关。此外，几种细胞因子，特别是 IL-8 和 IL-6，与 SARS-CoV-2 感染有显著关联。有趣的是，五种病毒感染中唯一共享的反应基因是 SERPINB1。蛋白质-蛋白质相互作用（PPI）分析揭示了 SARS-CoV-2 与其他病毒感染共享的高相互作用活性基因。研究结果表明，与类风湿关节炎、AGE-RAGE 信号系统、疟疾、乙型肝炎和甲型流感相关的遗传途径具有重要意义。我们发现，SARS-CoV-2 的感染病毒基因组转录组、宿主抗病毒反应的基因调节以及 GO 术语与 EBOV 更相似，而与 SARS、H1N1 和 MERS 相比则不那么相似。这项工作比较了高致病性病毒的病毒基因组特征，并为针对 SARS-CoV-2 的潜在治疗提供了有效靶点。
