Program in Bioinformatics and Integrative Biology; Program in Molecular Medicine
Amino Acids, Peptides, and Proteins | Biochemistry, Biophysics, and Structural Biology | Biodiversity | Ecology and Evolutionary Biology | Enzymes and Coenzymes | Genomics | Immunology and Infectious Disease | Virology | Virus Diseases
The novel coronavirus SARS-CoV-2 is the cause of Coronavirus Disease-2019 (COVID-19). The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of 410 vertebrates, including 252 mammals, to study cross-species conservation of ACE2 and its likelihood to function as a SARS-CoV-2 receptor. We designed a five-category ranking score based on the conservation properties of 25 amino acids important for the binding between receptor and virus, classifying all species from very high to very low. Only mammals fell into the medium to very high categories, and only catarrhine primates in the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 binding, and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (<0.1%) variants in 10/25 binding sites. In addition, we observed evidence of positive selection in ACE2 in multiple species, including bats. Utilized appropriately, our results may lead to the identification of intermediate host species for SARS-CoV-2, justify the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.
ACE2, COVID-19, SARS-CoV-2, comparative genomics, evolution, host range, species conservation
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
Damas J, Hughes GM, Keough KC, Painter CA, Persky NS, Corbo M, Hiller M, Koepfli KP, Pfenning AR, Zhao H, Genereux DP, Swofford R, Pollard KS, Ryder OA, Nweeia MT, Lindblad-Toh K, Teeling EC, Karlsson EK, Lewin HA. Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates. bioRxiv [Preprint]. 2020 Apr 18:2020.04.16.045302. doi: 10.1101/2020.04.16.045302. PMID: 32511356; PMCID: PMC7263403. Link to preprint on bioRxiv service
Damas J, Karlsson EK, Lewin HA. (2020). Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2020.04.16.045302. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1675
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Amino Acids, Peptides, and Proteins Commons, Biochemistry, Biophysics, and Structural Biology Commons, Biodiversity Commons, Ecology and Evolutionary Biology Commons, Enzymes and Coenzymes Commons, Genomics Commons, Immunology and Infectious Disease Commons, Virology Commons, Virus Diseases Commons