UMass Chan Medical School Faculty Publications

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Program in Bioinformatics and Integrative Biology; Program in Molecular Medicine

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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 (


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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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.

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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


Now published in PNAS, doi:10.1073/pnas.2010146117, and available in eScholarship@UMMS.

Full author list omitted for brevity. For the full list of authors, see preprint.

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Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.