Pathogenetic profiling of COVID-19 and SARS-like viruses

Link to article at PubMed

Brief Bioinform. 2020 Aug 11:bbaa173. doi: 10.1093/bib/bbaa173. Online ahead of print.


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.

PMID:32778874 | DOI:10.1093/bib/bbaa173

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