EVIDENCE | EBM Q: … “What medical evidence is published about the Expression of ACE2 in human tissues and implications for virus transmission?”

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Question

“What medical evidence is published about the Expression of ACE2 in human tissues and implications for virus transmission?”

Link(s) to Relevant Study(s)

  1. Published: 17 February 2020; Science Direct; Authors; Yun Chen,Yao Guo,Yihang Pan,Zhizhuang Joe Zhao; Publication: Biochemical and Biophysical Research Communications; Creative Commons: This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. You are not required to obtain permission to reuse this article; Publisher: Elsevier; Copyright © 2020, Elsevier; Structure analysis of the receptor binding of 2019-nCoV

Summary (or Screen Shot) of Relevant Data Specific to Question

  • Spike glycoprotein of 2019-nCoV may confer a strong ACE2 receptor binding.
  • Conserved expression of ACE2 suggests a wide range of natural hosts for 2019-nCoV.
  • Tissue expression of ACE2 suggests multiple routes of 2019-nCoV transmission.
  • 2019-nCoV is a newly identified coronavirus with high similarity to SARS-CoV. We performed a structural analysis of the receptor binding domain (RBD) of spike glycoprotein responsible for entry of coronaviruses into host cells. The RBDs from the two viruses share 72% identity in amino acid sequences, and molecular simulation reveals highly similar ternary structures. However, 2019-nCoV has a distinct loop with flexible glycyl residues replacing rigid prolyl residues in SARS-CoV. Molecular modeling revealed that 2019-nCoV RBD has a stronger interaction with angiotensin converting enzyme 2 (ACE2). A unique phenylalanine F486 in the flexible loop likely plays a major role because its penetration into a deep hydrophobic pocket in ACE2. ACE2 is widely expressed with conserved primary structures throughout the animal kingdom from fish, amphibians, reptiles, birds, to mammals. Structural analysis suggests that ACE2 from these animals can potentially bind RBD of 2019-nCoV, making them all possible natural hosts for the virus. 2019-nCoV is thought to be transmitted through respiratory droplets. However, since ACE2 is predominantly expressed in intestines, testis, and kidney, fecal-oral and other routes of transmission are also possible. Finally, antibodies and small molecular inhibitors that can block the interaction of ACE2 with RBD should be developed to combat the virus.

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