Pathogenetic profiling of COVID-19 and SARS-like viruses

Abstract

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.

Bioinformatics and system biology approach to identify the influences of COVID-19 on cardiovascular and hypertensive comorbidities

“…Angiotensin Converting Enzyme \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$2$\end{document} (ACE \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$2$\end{document} ) is known to play an important role in facilitating SARS-CoV- \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$2$\end{document} cell entry [ 26 , 44 , 46 , 65 ]. Expression of the ACE2 gene is reported in many human tissues including intestine, testis, kidneys, heart, and lungs [ 36 ].…”

Identification of angiotensin-converting enzyme 2 (ACE2) protein as the potential biomarker in SARS-CoV-2 infection-related lung cancer using computational analyses

“…Among four coronavirus genera α, β, γ, and δ, SARS-CoV-2 belongs to β-coronavirus. Additionally, the other two β coronaviruses are middle east respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV, but SARS-CoV-2 is more identical to SARS-CoV [ 2 , 3 ].…”

Preexisting and inducible endotoxemia as crucial contributors to the severity of COVID-19 outcomes

“…LPS up-regulates SHIP1, thereby inducing a compensatory response by suppression of TLR4 [ 22 ]. Important in this context, miR-155, whose expression was recently associated with the development of COVID-19 symptoms [ 23 ], is an established potent repressor of SHIP1 [ 24 ]. This microRNA is up-regulated during inflammation, is crucial for the development of fibrosis in different tissues, and can also serve as an oncogenic factor.…”