Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection

Biochem Biophys Res Commun. 2020 May 21;526(1):165-169. doi: 10.1016/j.bbrc.2020.03.047. Epub 2020 Mar 19.

Abstract

SARS-CoV-2 causes the recent global COVID-19 public health emergency. ACE2 is the receptor for both SARS-CoV-2 and SARS-CoV. To predict the potential host range of SARS-CoV-2, we analyzed the key residues of ACE2 for recognizing S protein. We found that most of the selected mammals including pets (dog and cat), pangolin and Circetidae mammals remained the most of key residues for association with S protein from SARS-CoV and SARS-CoV-2. The interaction interface between cat/dog/pangolin/Chinese hamster ACE2 and SARS-CoV/SARS-CoV-2 S protein was simulated through homology modeling. We identified that N82 in ACE2 showed a closer contact with SARS-CoV-2 S protein than M82 in human ACE2. Our finding will provide important insights into the host range of SARS-CoV-2 and a new strategy to design an optimized ACE2 for SARS-CoV-2 infection.

Keywords: ACE2; Host range; SARS-CoV-2; Spike protein; Structure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Betacoronavirus / physiology*
  • COVID-19
  • Coronavirus Infections / metabolism
  • Coronavirus Infections / transmission
  • Coronavirus Infections / virology
  • Humans
  • Mammals / classification
  • Mammals / metabolism
  • Models, Molecular
  • Pandemics
  • Peptidyl-Dipeptidase A / chemistry
  • Peptidyl-Dipeptidase A / metabolism*
  • Pneumonia, Viral / metabolism
  • Pneumonia, Viral / transmission
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Sequence Alignment
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Viral Tropism*

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2