Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates
UMass Chan Affiliations
Program in Bioinformatics and Integrative BiologyProgram in Molecular Medicine
Document Type
Journal ArticlePublication Date
2020-08-21Keywords
ACE2COVID-19
SARS-CoV-2
comparative genomics
species conservation
Amino Acids, Peptides, and Proteins
Ecology and Evolutionary Biology
Genetics and Genomics
Immunology and Infectious Disease
Infectious Disease
Structural Biology
Virus Diseases
Metadata
Show full item recordAbstract
The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of 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 ACE2 sequences from 410 vertebrate species, including 252 mammals, to study the conservation of ACE2 and its potential to be used as a receptor by SARS-CoV-2. We designed a five-category binding score based on the conservation properties of 25 amino acids important for the binding between ACE2 and the SARS-CoV-2 spike protein. Only mammals fell into the medium to very high categories and only catarrhine primates into 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 spike protein 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 (frequency < 0.001) variants in 10/25 binding sites. In addition, we found significant signals of selection and accelerated evolution in the ACE2 coding sequence across all mammals, and specific to the bat lineage. Our results, if confirmed by additional experimental data, may lead to the identification of intermediate host species for SARS-CoV-2, guide the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.Source
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. Proc Natl Acad Sci U S A. 2020 Aug 21:202010146. doi: 10.1073/pnas.2010146117. Epub ahead of print. PMID: 32826334. Link to article on publisher's site
DOI
10.1073/pnas.2010146117Permanent Link to this Item
http://hdl.handle.net/20.500.14038/27318PubMed ID
32826334Notes
This article is based on a previously available preprint.
Full author list omitted for brevity. For the full list of authors, see article.
Related Resources
Rights
Copyright © 2020 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1073/pnas.2010146117
Scopus Count
Except where otherwise noted, this item's license is described as Copyright © 2020 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).