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Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates

Joana Damas1, Graham M Hughes2, Kathleen C Keough3,4

  • 1The Genome Center, University of California, Davis, CA 95616.

Proceedings of the National Academy of Sciences of the United States of America
|August 23, 2020
PubMed

Insights

Researchers analyzed angiotensin I converting enzyme 2 (ACE2) in 410 species to assess SARS-CoV-2 infection risk. Mammals, especially primates, show high binding potential, indicating elevated risk for COVID-19.

Area of Science:

  • Comparative genomics
  • Virology
  • Evolutionary biology

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19.
  • Angiotensin I converting enzyme 2 (ACE2) is the primary receptor for SARS-CoV-2.
  • Understanding species susceptibility is crucial for transmission and control.

Purpose of the Study:

  • To investigate the conservation of ACE2 across vertebrate species.
  • To evaluate the potential of ACE2 as a SARS-CoV-2 receptor.
  • To identify species at high risk for SARS-CoV-2 infection.

Main Methods:

  • Analysis of ACE2 sequences from 410 vertebrate species.
  • Development of a five-category binding score based on 25 key amino acids.
  • Protein structural analysis to predict binding disruption.
  • Examination of human population data for ACE2 variants.
  • Detection of selection and accelerated evolution signals in ACE2.

Main Results:

  • Mammals exhibited medium to very high ACE2 binding scores, with catarrhine primates in the very high category.
  • Protein structural analysis correlated unfavorable amino acid changes with binding scores.
  • Rare variants (<0.001) were found in human ACE2 binding sites.
  • Significant signals of selection and accelerated evolution were identified in mammalian and bat ACE2 sequences.

Conclusions:

  • Mammals, particularly primates, are at high risk for SARS-CoV-2 infection due to ACE2 binding potential.
  • Findings may help identify intermediate host species and inform animal model selection for COVID-19 research.
  • Results could aid in the conservation of at-risk animal populations.
Keywords:
ACE2COVID-19SARS-CoV-2comparative genomicsspecies conservation

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