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Updated: Dec 19, 2025

Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
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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, Davis, CA 95616, USA.

Biorxiv : the Preprint Server for Biology
|June 9, 2020
PubMed

Insights

This study analyzed angiotensin I converting enzyme 2 (ACE2) conservation across 410 vertebrate species to assess SARS-CoV-2 infection risk. Catarrhine primates show very high ACE2 conservation, indicating elevated risk for COVID-19 infection.

Area of Science:

  • Comparative genomics and molecular biology.
  • Virology and zoonotic disease research.

Background:

  • The novel coronavirus SARS-CoV-2 causes COVID-19, with its transmission influenced by the ACE2 receptor.
  • Understanding ACE2 receptor conservation across species is crucial for identifying transmission routes and susceptible populations.

Approach:

  • A dataset of 410 vertebrates, including 252 mammals, was analyzed for ACE2 conservation.
  • A five-category ranking score was developed based on 25 key amino acids for ACE2-SARS-CoV-2 binding.
  • Protein structural analysis and human population data were used to assess binding disruption and variant frequencies.

Key Points:

  • Mammals exhibited medium to very high ACE2 conservation, with catarrhine primates in the very high category, suggesting significant COVID-19 risk.
  • Amino acid changes impacting ACE2/SARS-CoV-2 binding were correlated with the binding score.
  • Rare variants (<0.1%) were found in human ACE2 binding sites, with evidence of positive selection in ACE2 in species like bats.

Conclusions:

  • The findings identify high-risk species for SARS-CoV-2 infection, aiding in the selection of appropriate animal models for COVID-19 research.
  • Results can inform strategies for identifying intermediate host species and contribute to wildlife conservation efforts.
Keywords:
ACE2COVID-19SARS-CoV-2comparative genomicsevolutionhost rangespecies conservation

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