The novel coronavirus (2019-nCoV) has recently emerged, causing COVID-19 outbreaks and significant societal/global disruption. Importantly, COVID-19 infection resembles SARS-like complications. However, the lack of knowledge about the underlying genetic mechanisms of COVID-19 warrants the development of prospective control measures. In this study, we employed whole-genome alignment and digital DNA–DNA hybridization analyses to assess genomic linkage between 2019-nCoV and other coronaviruses. To understand the pathogenetic behavior of 2019-nCoV, we compared gene expression datasets of viral infections closest to 2019-nCoV with four COVID-19 clinical presentations followed by functional enrichment of shared dysregulated genes. Potential chemical antagonists were also identified using protein–chemical interaction analysis. Based on phylogram analysis, the 2019-nCoV was found genetically closest to SARS-CoVs. In addition, we identified 562 upregulated and 738 downregulated genes (adj. P ≤ 0.05) with SARS-CoV infection. Among the dysregulated genes, SARS-CoV shared ≤19 upregulated and ≤22 downregulated genes with each of different COVID-19 complications. Notably, upregulation of BCL6 and PFKFB3 genes was common to SARS-CoV, pneumonia and severe acute respiratory syndrome, while they shared CRIP2, NSG1 and TNFRSF21 genes in downregulation. Besides, 14 genes were common to different SARS-CoV comorbidities that might influence COVID-19 disease. We also observed similarities in pathways that can lead to COVID-19 and SARS-CoV diseases. Finally, protein–chemical interactions suggest cyclosporine, resveratrol and quercetin as promising drug candidates against COVID-19 as well as other SARS-like viral infections. The pathogenetic analyses, along with identified biomarkers, signaling pathways and chemical antagonists, could prove useful for novel drug development in the fight against the current global 2019-nCoV pandemic.

中文翻译：

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COVID-19 和 SARS 类病毒的病原学分析

新型冠状病毒 (2019-nCoV) 最近出现，导致了 COVID-19 爆发和严重的社会/全球破坏。重要的是，COVID-19 感染类似于 SARS 样并发症。然而，由于缺乏对 COVID-19 潜在遗传机制的了解，需要制定前瞻性控制措施。在这项研究中，我们采用全基因组比对和数字 DNA-DNA 杂交分析来评估 2019-nCoV 与其他冠状病毒之间的基因组联系。为了了解 2019-nCoV 的致病行为，我们将最接近 2019-nCoV 的病毒感染的基因表达数据集与四种 COVID-19 临床表现进行了比较，然后对共享失调基因进行了功能富集。还通过蛋白质-化学相互作用分析鉴定了潜在的化学拮抗剂。根据系统图分析，发现 2019-nCoV 在基因上最接近 SARS-CoV。此外，我们还发现了 SARS-CoV 感染时 562 个上调基因和 738 个下调基因（调整P  ≤ 0.05）。在失调的基因中，SARS-CoV 与每种不同的 COVID-19 并发症共有 ≤19 个上调基因和 ≤22 个下调基因。值得注意的是， BCL6和PFKFB3基因的上调在 SARS-CoV、肺炎和严重急性呼吸综合征中很常见，而它们共享CRIP2、NSG1和TNFRSF21基因的下调。此外，14 个基因是可能影响 COVID-19 疾病的不同 SARS-CoV 合并症的常见基因。我们还观察到导致 COVID-19 和 SARS-CoV 疾病的途径有相似之处。最后，蛋白质-化学相互作用表明环孢菌素、白藜芦醇和槲皮素是对抗 COVID-19 以及其他 SARS 类病毒感染的有希望的候选药物。发病机制分析以及已确定的生物标志物、信号通路和化学拮抗剂可能有助于开发抗击当前全球 2019-nCoV 大流行的新药。