Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2

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, putative functions, and transcriptional regulation. The small intestine expressed higher levels of ACE2 than any other organ. The large intestine, kidney and testis showed moderate signals, whereas the signal was weak in the lung specimens. Single cell RNA-Seq data indicated positive signals along the respiratory tract in the key protective cell types including the goblet and ciliary epithelial cells, as well as in the endothelial cells and type I pneumocytes. Gene ontology analysis suggested that, besides its classical role in renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/blood vessel morphogenesis. A novel tool for the prediction of transcription factor binding sites identified several putative sites for determined transcription factors within the ACE2 gene promoter. Our results also confirmed that age and gender play no significant role in the regulation of ACE2 mRNA expression in the lung.

ACE2, TMPRSS2 distribution and extrapulmonary organ injury in patients with COVID-19

“…However, clinicians still should assess the reproductive function of male COVID-19 patients for prognosis. It was also found that the expression of ACE2 in adipose tissue was relatively high, which indicated that infection of SARS-CoV-2 may be related with obesity [ 34 , 35 ].…”

“…The mRNA expressions of ACE2 in different human organs were analyzed and the results showed that ACE2 was expressed in the heart [ 27 , 34 ]. Furthermore, Chen et al analyzed the feature of ACE2 expressions among cardiac cell types and found that ACE2 was specifically expressed in pericyte [ 35 ].…”

SARS-CoV-2 induces transcriptional signatures in human lung epithelial cells that promote lung fibrosis

“…We have found that ACE2 mRNA expression is mainly found in gastrointestinal (GI) tract and the small intestine has the highest level of ACE2 levels compared to other organs in this study. Diarrhea is one of major symptoms of COVID-19 and high numbers of ACE2 positive small intestine cells occur in COVID-19 patients [43]. This indicates that SARS-CoV-2 also may also affect the GI tract through the ACE2 receptor.…”

Intestinal receptor of SARS-CoV-2 in inflamed IBD tissue is downregulated by HNF4A in ileum and upregulated by interferon regulating factors in colon

“…ACE2 expression in the gastrointestinal tract is primarily found in absorptive enterocytes, 7,37 which could indirectly be confirmed through the significant correlation (p<2.2E-16) between mucosal ACE2 and several epithelial marker genes (APOA1, SI, FABP6, ENPEP) (Supplementary Figure S2). To further examine the expression of genes associated with risk of SARS-CoV-2 infection in IBD patients, we employed sc-RNA seq to profile transmural biopsies of (un)inflamed regions of resected tissue from six CD patients undergoing ileocaecal resection.…”