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dc.contributor.authorDamas, Joana
dc.contributor.authorHughes, Graham M.
dc.contributor.authorKeough, Kathleen C.
dc.contributor.authorPainter, Corrie A.
dc.contributor.authorPersky, Nicole S.
dc.contributor.authorCorbo, Marco
dc.contributor.authorHiller, Michael
dc.contributor.authorKoepfli, Klaus-Peter
dc.contributor.authorPfenning, Andreas R.
dc.contributor.authorZhao, Huabin
dc.contributor.authorGenereux, Diane P.
dc.contributor.authorSwofford, Ross
dc.contributor.authorPollard, Katherine S.
dc.contributor.authorRyder, Oliver A.
dc.contributor.authorNweeia, Martin T.
dc.contributor.authorLindblad-Toh, Kerstin
dc.contributor.authorTeeling, Emma C.
dc.contributor.authorKarlsson, Elinor K.
dc.contributor.authorLewin, Harris A.
dc.date.accessioned2021-03-19T17:31:19Z
dc.date.available2021-03-19T17:31:19Z
dc.date.issued2020
dc.identifier.issn0027-8424, 1091-6490
dc.identifier.doi10.1073/pnas.2010146117
dc.identifier.urihttp://hdl.handle.net/20.500.12634/945
dc.descriptionCoronavirus SARS-CoV-2 is the cause of COVID-19, a pandemic threatening millions of human lives and the global economy. The main receptor of SARS-CoV-2, called ACE2, can be studied to understand the routes of transmission and sensitivity across species. 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, identifying a large number of mammals that can potentially be infected by this route. Among the species we found with the highest risk for SARS-CoV-2 infection are wildlife and endangered species. These species represent an opportunity for spillover of SARS-CoV-2 from humans to other susceptible animals. Our results, if confirmed by additional experimental data, may lead to the identification of intermediate host species for SARS-CoV-2 and assist the conservation of animals both in native habitats and in human care.
dc.description.abstractThe 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.
dc.language.isoen
dc.relation.urlhttps://www.pnas.org/content/early/2020/08/20/2010146117
dc.rightsCopyright © 2020 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectVIROLOGY
dc.subjectIMMUNOLOGY
dc.subjectGENOMICS
dc.subjectWILDLIFE CONSERVATION
dc.subjectINFECTION
dc.subjectDISEASES
dc.subjectVERTEBRATES
dc.subjectMAMMALS
dc.subjectPRIMATES
dc.subjectBATS
dc.subjectRESEARCH
dc.subjectTHERAPY
dc.subjectVETERINARY MEDICINE
dc.subjectENDANGERED SPECIES
dc.subjectANIMAL-HUMAN RELATIONSHIPS
dc.subjectEVOLUTION
dc.titleBroad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates
dc.typeArticle
dc.source.journaltitleProceedings of the National Academy of Sciences
dc.source.volume117
dc.source.issue6
dc.source.beginpage22311
dc.source.endpage22322
refterms.dateFOA2021-03-19T17:35:51Z
html.description.abstractThe 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.
dc.source.conference


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Copyright © 2020 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
Except where otherwise noted, this item's license is described as Copyright © 2020 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).