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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 09 08; 117(36):22311-22322.PN

Abstract

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.

Authors+Show Affiliations

The Genome Center, University of California, Davis, CA 95616.School of Biology and Environmental Science, University College Dublin, Belfield, Dublin 4, Ireland.Graduate Program in Pharmaceutical Sciences and Pharmacogenomics, Quantitative Biosciences Consortium, University of California, San Francisco, CA 94117. Gladstone Institute of Data Science and Biotechnology, San Francisco, CA 94158.Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142.Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142.The Genome Center, University of California, Davis, CA 95616.Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany. Max Planck Institute for the Physics of Complex Systems, 01187 Dresden, Germany. Center for Systems Biology Dresden, 01307 Dresden, Germany.Center for Species Survival, Smithsonian Conservation Biology Institute, National Zoological Park, Front Royal, VA 22630.Department of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213.Department of Ecology, Tibetan Centre for Ecology and Conservation at WHU-TU, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China. College of Science, Tibet University, Lhasa 850000, China.Broad Institute of MIT and Harvard, Cambridge, MA 02142.Broad Institute of MIT and Harvard, Cambridge, MA 02142.Gladstone Institute of Data Science and Biotechnology, San Francisco, CA 94158. Department of Epidemiology & Biostatistics, Institute for Computational Health Sciences, and Institute for Human Genetics, University of California, San Francisco, CA 94158. Chan Zuckerberg Biohub, San Francisco, CA 94158.San Diego Zoo Institute for Conservation Research, Escondido, CA 92027. Department of Evolution, Behavior, and Ecology, Division of Biology, University of California San Diego, La Jolla, CA 92093.Department of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine, Boston, MA 02115. School of Dental Medicine, Case Western Reserve University, Cleveland, OH 44106. Marine Mammal Program, Department of Vertebrate Zoology, Smithsonian Institution, Washington, DC 20002.Broad Institute of MIT and Harvard, Cambridge, MA 02142. Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden.School of Biology and Environmental Science, University College Dublin, Belfield, Dublin 4, Ireland.Broad Institute of MIT and Harvard, Cambridge, MA 02142. Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01655. Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655.The Genome Center, University of California, Davis, CA 95616; Lewin@ucdavis.edu. Department of Evolution and Ecology, University of California, Davis, CA 95616. John Muir Institute for the Environment, University of California, Davis, CA 95616.

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

32826334

Citation

Damas, Joana, et al. "Broad Host Range of SARS-CoV-2 Predicted By Comparative and Structural Analysis of ACE2 in Vertebrates." Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 36, 2020, pp. 22311-22322.
Damas J, Hughes GM, Keough KC, et al. Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates. Proc Natl Acad Sci USA. 2020;117(36):22311-22322.
Damas, J., Hughes, G. M., Keough, K. C., Painter, C. A., Persky, N. S., Corbo, M., Hiller, M., Koepfli, K. P., Pfenning, A. R., Zhao, H., Genereux, D. P., Swofford, R., Pollard, K. S., Ryder, O. A., Nweeia, M. T., Lindblad-Toh, K., Teeling, E. C., Karlsson, E. K., & Lewin, H. A. (2020). Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates. Proceedings of the National Academy of Sciences of the United States of America, 117(36), 22311-22322. https://doi.org/10.1073/pnas.2010146117
Damas J, et al. Broad Host Range of SARS-CoV-2 Predicted By Comparative and Structural Analysis of ACE2 in Vertebrates. Proc Natl Acad Sci USA. 2020 09 8;117(36):22311-22322. PubMed PMID: 32826334.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates. AU - Damas,Joana, AU - Hughes,Graham M, AU - Keough,Kathleen C, AU - Painter,Corrie A, AU - Persky,Nicole S, AU - Corbo,Marco, AU - Hiller,Michael, AU - Koepfli,Klaus-Peter, AU - Pfenning,Andreas R, AU - Zhao,Huabin, AU - Genereux,Diane P, AU - Swofford,Ross, AU - Pollard,Katherine S, AU - Ryder,Oliver A, AU - Nweeia,Martin T, AU - Lindblad-Toh,Kerstin, AU - Teeling,Emma C, AU - Karlsson,Elinor K, AU - Lewin,Harris A, Y1 - 2020/08/21/ PY - 2020/8/23/pubmed PY - 2020/9/18/medline PY - 2020/8/23/entrez KW - ACE2 KW - COVID-19 KW - SARS-CoV-2 KW - comparative genomics KW - species conservation SP - 22311 EP - 22322 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 117 IS - 36 N2 - 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. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/32826334/Broad_host_range_of_SARS_CoV_2_predicted_by_comparative_and_structural_analysis_of_ACE2_in_vertebrates_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&amp;pmid=32826334 DB - PRIME DP - Unbound Medicine ER -