{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:13:33Z","timestamp":1772172813812,"version":"3.50.1"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Molecular Sciences Software Institute","award":["ACI-1547580"],"award-info":[{"award-number":["ACI-1547580"]}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM122543"],"award-info":[{"award-number":["R35GM122543"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM122543"],"award-info":[{"award-number":["R35GM122543"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["03Z22HN23"],"award-info":[{"award-number":["03Z22HN23"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Regional Development Fund for Saxony-Anhalt","award":["ZS\/2016\/04\/78115"],"award-info":[{"award-number":["ZS\/2016\/04\/78115"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 31 million people in more than 180 countries worldwide. Like other coronaviruses, SARS-CoV-2 is thought to have been transmitted to humans from wild animals. Given the scale and widespread geographical distribution of the current pandemic and confirmed cases of cross-species transmission, the question of the extent to which this transmission is possible emerges, as well as what molecular features distinguish susceptible from non-susceptible animal species. Here, we investigated the structural properties of several ACE2 orthologs bound to the SARS-CoV-2 spike protein. We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Our models also allow us to predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes. Finally, our study provides a blueprint for modeling viral-host protein interactions and highlights several important considerations when designing these computational studies and analyzing their results.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1008449","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T13:28:43Z","timestamp":1607002123000},"page":"e1008449","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":53,"title":["Insights on cross-species transmission of SARS-CoV-2 from structural modeling"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9796-3193","authenticated-orcid":true,"given":"Jo\u00e3o P. G. L. M.","family":"Rodrigues","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4868-6593","authenticated-orcid":true,"given":"Susana","family":"Barrera-Vilarmau","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9113-0622","authenticated-orcid":true,"given":"Jo\u00e3o","family":"M. C. Teixeira","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0195-0094","authenticated-orcid":true,"given":"Marija","family":"Sorokina","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5910-649X","authenticated-orcid":true,"given":"Elizabeth","family":"Seckel","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1463-8422","authenticated-orcid":true,"given":"Panagiotis L.","family":"Kastritis","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8414-7397","authenticated-orcid":true,"given":"Michael","family":"Levitt","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"key":"pcbi.1008449.ref001","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S1473-3099(20)30120-1","article-title":"An interactive web-based dashboard to track COVID-19 in real time","volume":"20","author":"E Dong","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"pcbi.1008449.ref002","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/s41591-020-0820-9","article-title":"The proximal origin of SARS-CoV-2","volume":"26","author":"KG Andersen","year":"2020","journal-title":"Nat Med"},{"key":"pcbi.1008449.ref003","unstructured":"A cat appears to have caught the coronavirus, but it\u2019s complicated. In: Science News [Internet]. 31 Mar 2020 [cited 2 Jun 2020]. Available: https:\/\/www.sciencenews.org\/article\/cats-animals-pets-coronavirus-covid19"},{"key":"pcbi.1008449.ref004","unstructured":"Confirmation of COVID-19 in Two Pet Cats in New York | CDC Online Newsroom | CDC. 22 Apr 2020 [cited 2 Jun 2020]. Available: https:\/\/www.cdc.gov\/media\/releases\/2020\/s0422-covid-19-cats-NYC.html"},{"key":"pcbi.1008449.ref005","unstructured":"Mink infected two humans with coronavirus: Dutch government. Reuters. 25 May 2020. Available: https:\/\/www.reuters.com\/article\/us-health-coronavirus-netherlands-mink-idUSKBN23112K. Accessed 2 Jun 2020."},{"key":"pcbi.1008449.ref006","unstructured":"Seven more big cats test positive for coronavirus at Bronx Zoo. In: Animals [Internet]. 22 Apr 2020 [cited 2 Jun 2020]. Available: https:\/\/www.nationalgeographic.com\/animals\/2020\/04\/tiger-coronavirus-covid19-positive-test-bronx-zoo\/"},{"key":"pcbi.1008449.ref007","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1126\/science.abb7015","article-title":"Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS\u2013coronavirus 2","volume":"368","author":"J Shi","year":"2020","journal-title":"Science"},{"key":"pcbi.1008449.ref008","article-title":"Potential host range of multiple SARS-like coronaviruses and an improved ACE2-Fc variant that is potent against both SARS-CoV-2 and SARS-CoV-1","author":"Y Li","year":"2020","journal-title":"Microbiology"},{"key":"pcbi.1008449.ref009","article-title":"Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility","author":"JF-W Chan","journal-title":"Clin Infect Dis"},{"key":"pcbi.1008449.ref010","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.cell.2020.03.045","article-title":"Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2","volume":"181","author":"Q Wang","year":"2020","journal-title":"Cell"},{"key":"pcbi.1008449.ref011","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41586-020-2180-5","article-title":"Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor","volume":"581","author":"J Lan","year":"2020","journal-title":"Nature"},{"key":"pcbi.1008449.ref012","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1126\/science.abb2762","article-title":"Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2","volume":"367","author":"R Yan","year":"2020","journal-title":"Science"},{"key":"pcbi.1008449.ref013","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/s41586-020-2179-y","article-title":"Structural basis of receptor recognition by SARS-CoV-2","volume":"581","author":"J Shang","year":"2020","journal-title":"Nature"},{"key":"pcbi.1008449.ref014","article-title":"The sequence of human ACE2 is suboptimal for binding the S spike protein of SARS coronavirus 2","author":"E. 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