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Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2.
Barker, Harlan; Parkkila, Seppo.
  • Barker H; Faculty of Medicine and Health Technology, Tampere University and Fimlab Ltd, Tampere University Hospital, Tampere, Finland.
  • Parkkila S; Faculty of Medicine and Health Technology, Tampere University and Fimlab Ltd, Tampere University Hospital, Tampere, Finland.
PLoS One ; 15(10): e0240647, 2020.
Article in English | MEDLINE | ID: covidwho-895060
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ABSTRACT
The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics tools to computationally characterize ACE2 by determining its cell-specific expression in trachea, lung, and small intestine, derive its putative functions, and predict transcriptional regulation. The small intestine expressed higher levels of ACE2 mRNA than any other organ. By immunohistochemistry, duodenum, kidney and testis showed strong signals, whereas the signal was weak in the respiratory tract. Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. Gene ontology analysis suggested that, besides its classical role in the renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/blood vessel morphogenesis. Using a novel tool for the prediction of transcription factor binding sites we identified several putative binding sites within two tissue-specific promoters of the ACE2 gene as well as a new putative short form of ACE2. These include several interferon-stimulated response elements sites for STAT1, IRF8, and IRF9. Our results also confirmed that age and gender play no significant role in the regulation of ACE2 mRNA expression in the lung.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Receptors, Virus / Coronavirus Infections / Peptidyl-Dipeptidase A / Computational Biology / Pandemics / Betacoronavirus Type of study: Prognostic study Limits: Female / Humans / Male Language: English Journal: PLoS One Journal subject: Science / Medicine Year: 2020 Document Type: Article Affiliation country: Journal.pone.0240647

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Receptors, Virus / Coronavirus Infections / Peptidyl-Dipeptidase A / Computational Biology / Pandemics / Betacoronavirus Type of study: Prognostic study Limits: Female / Humans / Male Language: English Journal: PLoS One Journal subject: Science / Medicine Year: 2020 Document Type: Article Affiliation country: Journal.pone.0240647