Predicting mammalian species at risk of being infected by SARS-CoV-2 from an ACE2 perspective

Sci Rep. 2021 Jan 18;11(1):1702. doi: 10.1038/s41598-020-80573-x.

Abstract

SARS-CoV-2 can transmit efficiently in humans, but it is less clear which other mammals are at risk of being infected. SARS-CoV-2 encodes a Spike (S) protein that binds to human ACE2 receptor to mediate cell entry. A species with a human-like ACE2 receptor could therefore be at risk of being infected by SARS-CoV-2. We compared between 132 mammalian ACE2 genes and between 17 coronavirus S proteins. We showed that while global similarities reflected by whole ACE2 gene alignments are poor predictors of high-risk mammals, local similarities at key S protein-binding sites highlight several high-risk mammals that share good ACE2 homology with human. Bats are likely reservoirs of SARS-CoV-2, but there are other high-risk mammals that share better ACE2 homologies with human. Both SARS-CoV-2 and SARS-CoV are closely related to bat coronavirus. Yet, among host-specific coronaviruses infecting high-risk mammals, key ACE2-binding sites on S proteins share highest similarities between SARS-CoV-2 and Pangolin-CoV and between SARS-CoV and Civet-CoV. These results suggest that direct coronavirus transmission from bat to human is unlikely, and that rapid adaptation of a bat SARS-like coronavirus in different high-risk intermediate hosts could have allowed it to acquire distinct high binding potential between S protein and human-like ACE2 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / chemistry
  • Angiotensin-Converting Enzyme 2 / classification
  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / metabolism*
  • Animals
  • Binding Sites
  • COVID-19 / pathology
  • COVID-19 / transmission
  • COVID-19 / virology
  • Chiroptera / genetics
  • Humans
  • Mammals
  • Phylogeny
  • Protein Binding
  • Risk
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / physiology*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / classification
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / metabolism*

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Angiotensin-Converting Enzyme 2