{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T12:56:59Z","timestamp":1777899419778,"version":"3.51.4"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":44,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000884","name":"Cancer Research Institute","doi-asserted-by":"publisher","award":["CRI4017"],"award-info":[{"award-number":["CRI4017"]}],"id":[{"id":"10.13039\/100000884","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    SARS-CoV-2 infection of humans and its spillover into new species illustrates the need for effective predictive tools designed to identify host ranges of emerging zoonotic viruses. We hypothesized that host receptor sequence similarity across animals could be leveraged to identify species at risk for cross-species virus transmission. We developed a flexible computational pipeline,\n                    <jats:bold>M<\/jats:bold>\n                    ulti-\n                    <jats:bold>r<\/jats:bold>\n                    eference\n                    <jats:bold>S<\/jats:bold>\n                    imilarity\n                    <jats:bold>A<\/jats:bold>\n                    nalysis of\n                    <jats:bold>R<\/jats:bold>\n                    eceptor\n                    <jats:bold>S<\/jats:bold>\n                    equences (MrSARS), to compare homologous virus-binding receptor sequences to multiple reference host sequences. MrSARS applies an aggregate similarity score to each examined receptor sequence and categorizes them as highly or moderately susceptible, or resistant to infection. We used the sarbecovirus receptor angiotensin converting enzyme 2 (ACE2) as a model to test MrSARS predictions because ACE2 has been extensively sequenced, and its interaction with SARS-CoV and SARS-CoV-2 glycoproteins characterized. We analyzed 825 vertebrate ACE2 sequences and determined that primates and even-toed ungulates ranked highest among susceptible species. We tested these predictions by infecting 293T cells, transiently expressing ACE2 from confirmed, putatively susceptible, and resistant species, with SARS-CoV-2 variant and SARS-CoV-related glycoprotein-pseudotyped VSV reporter viruses. These experiments correlated with MrSARS susceptibility predictions and existing literature. Our study illustrates that receptor sequence information from multiple susceptible species can identify potential host ranges of circulating viruses.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-41410-9","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:04:52Z","timestamp":1773817492000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systematic multi-reference vertebrate ACE2 sequence similarity analysis predicts species susceptibility to SARS-related sarbecoviruses"],"prefix":"10.1038","volume":"16","author":[{"given":"John A.","family":"Frank","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric Xu","family":"Gan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William Brenham","family":"Hooper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel Madeleine","family":"Ott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko","family":"Iwasaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"41410_CR1","unstructured":"Organization, W. H. Zoonoses. Zoonoses. Fact Sheet (2020). at https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/zoonoses"},{"key":"41410_CR2","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1146\/annurev-animal-062922-060125","volume":"11","author":"O Tomori","year":"2023","unstructured":"Tomori, O. & Oluwayelu, D. O. Domestic animals as potential reservoirs of zoonotic viral diseases. Annu. Rev. Anim. Biosci. 11, 33\u201355 (2023).","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"41410_CR3","doi-asserted-by":"publisher","first-page":"2100009","DOI":"10.2807\/1560-7917.ES.2021.26.5.210009","volume":"26","author":"HD Larsen","year":"2021","unstructured":"Larsen, H. D. et al. Preliminary report of an outbreak of SARS-CoV-2 in mink and mink farmers associated with community spread, Denmark, June to November 2020. Euro. Surveill. 26, 2100009 (2021).","journal-title":"Euro. Surveill."},{"key":"41410_CR4","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/s41577-023-00868-8","volume":"23","author":"F Krammer","year":"2023","unstructured":"Krammer, F. & Schultz-Cherry, S. We need to keep an eye on avian influenza. Nat. Rev. Immunol. 23, 267\u2013268 (2023).","journal-title":"Nat. Rev. Immunol."},{"key":"41410_CR5","doi-asserted-by":"publisher","first-page":"160","DOI":"10.20506\/rst.19.1.1202","volume":"19","author":"MNM Nor","year":"2000","unstructured":"Nor, M. N. M., Gan, C. H. & Ong, B. L. Nipah virus infection of pigs in peninsular Malaysia: -EN- -FR- -ES-. Rev. Sci. Tech. l\u2019OIE 19, 160\u2013165 (2000).","journal-title":"Rev. Sci. Tech. l\u2019OIE"},{"key":"41410_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3201\/eid2903.221079","volume":"29","author":"NM Vora","year":"2023","unstructured":"Vora, N. M. et al. Interventions to reduce risk for pathogen spillover and early disease spread to prevent outbreaks, epidemics, and pandemics - volume 29, number 3\u2014march 2023 - emerging infectious diseases journal - CDC. Emerg. Infect. Dis. 29, 1\u20139 (2023).","journal-title":"Emerg. Infect. Dis."},{"key":"41410_CR7","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1038\/d41586-022-01312-y","volume":"605","author":"NM Vora","year":"2022","unstructured":"Vora, N. M. et al. Want to prevent pandemics? Stop spillovers. Nature 605, 419\u2013422 (2022).","journal-title":"Nature"},{"key":"41410_CR8","doi-asserted-by":"publisher","first-page":"e00397-18","DOI":"10.1128\/mSphere.00397-18","volume":"3","author":"MR Ingala","year":"2018","unstructured":"Ingala, M. R., Simmons, N. B. & Perkins, S. L. Bats are an untapped system for understanding microbiome evolution in mammals. mSphere 3, e00397-18 (2018).","journal-title":"mSphere"},{"key":"41410_CR9","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1038\/s41559-021-01407-1","volume":"5","author":"H Yan","year":"2021","unstructured":"Yan, H. et al. ACE2 receptor usage reveals variation in susceptibility to SARS-CoV and SARS-CoV-2 infection among bat species. Nat. Ecol. Evol. 5, 600\u2013608 (2021).","journal-title":"Nat. Ecol. Evol."},{"key":"41410_CR10","doi-asserted-by":"publisher","first-page":"e2025373118","DOI":"10.1073\/pnas.2025373118","volume":"118","author":"Y Liu","year":"2021","unstructured":"Liu, Y. et al. Functional and genetic analysis of viral receptor ACE2 orthologs reveals a broad potential host range of SARS-CoV-2. Proc Nat. Acad. Sci. 118, e2025373118 (2021).","journal-title":"Proc Nat. Acad. Sci."},{"key":"41410_CR11","doi-asserted-by":"crossref","unstructured":"Li, Y. et al. SARS-CoV-2 and three related coronaviruses utilize multiple ACE2 orthologs and are potently blocked by an improved ACE2-Ig. J Virol 94, (2020).","DOI":"10.1128\/JVI.01283-20"},{"key":"41410_CR12","doi-asserted-by":"publisher","unstructured":"Si, J. et al. Sarbecovirus RBD indels and specific residues dictating ACE2 multi-species adaptiveness. bioRxiv 2024.02.11.579781 (2024). https:\/\/doi.org\/10.1101\/2024.02.11.579781","DOI":"10.1101\/2024.02.11.579781"},{"key":"41410_CR13","doi-asserted-by":"publisher","first-page":"e3001390","DOI":"10.1371\/journal.pbio.3001390","volume":"19","author":"N Mollentze","year":"2021","unstructured":"Mollentze, N., Babayan, S. A. & Streicker, D. G. Identifying and prioritizing potential human-infecting viruses from their genome sequences. PLoS. Biol. 19, e3001390 (2021).","journal-title":"PLoS. Biol."},{"key":"41410_CR14","doi-asserted-by":"publisher","first-page":"e80329","DOI":"10.7554\/eLife.80329","volume":"11","author":"N Mollentze","year":"2022","unstructured":"Mollentze, N., Keen, D., Munkhbayar, U., Biek, R. & Streicker, D. G. Variation in the ACE2 receptor has limited utility for SARS-CoV-2 host prediction. Elife 11, e80329 (2022).","journal-title":"Elife"},{"key":"41410_CR15","doi-asserted-by":"publisher","first-page":"e1009149","DOI":"10.1371\/journal.ppat.1009149","volume":"17","author":"L Brierley","year":"2021","unstructured":"Brierley, L. & Fowler, A. Predicting the animal hosts of coronaviruses from compositional biases of spike protein and whole genome sequences through machine learning. PLoS Pathog. 17, e1009149 (2021).","journal-title":"PLoS Pathog."},{"key":"41410_CR16","doi-asserted-by":"publisher","first-page":"20211651","DOI":"10.1098\/rspb.2021.1651","volume":"288","author":"IR Fischhoff","year":"2021","unstructured":"Fischhoff, I. R., Castellanos, A. A., Rodrigues, J. P. G. L. M., Varsani, A. & Han, B. A. Predicting the zoonotic capacity of mammals to transmit SARS-CoV-2. Proc. R. Soc. B Biol. Sci. 288, 20211651 (2021).","journal-title":"Proc. R. Soc. B Biol. Sci."},{"key":"41410_CR17","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/s41564-020-0688-y","volume":"5","author":"M Letko","year":"2020","unstructured":"Letko, M., Marzi, A. & Munster, V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat. Microbiol. 5, 562\u2013569 (2020).","journal-title":"Nat. Microbiol."},{"key":"41410_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04464-z","author":"TN Starr","year":"2022","unstructured":"Starr, T. N. et al. ACE2 binding is an ancestral and evolvable trait of sarbecoviruses. Nature https:\/\/doi.org\/10.1038\/s41586-022-04464-z (2022).","journal-title":"Nature"},{"key":"41410_CR19","doi-asserted-by":"publisher","first-page":"e3000217","DOI":"10.1371\/journal.pbio.3000217","volume":"17","author":"CJ Warren","year":"2019","unstructured":"Warren, C. J. & Sawyer, S. L. How host genetics dictates successful viral zoonosis. PLoS Biol. 17, e3000217 (2019).","journal-title":"PLoS Biol."},{"key":"41410_CR20","unstructured":"Kans, J. Entrez Direct: E-utilities on the Unix Command Line. (2020). at https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK179288\/"},{"key":"41410_CR21","doi-asserted-by":"publisher","first-page":"D20","DOI":"10.1093\/nar\/gkab1112","volume":"50","author":"EW Sayers","year":"2021","unstructured":"Sayers, E. W. et al. Database resources of the national center for biotechnology information. Nucl. Acids Res. 50, D20\u2013D26 (2021).","journal-title":"Nucl. Acids Res."},{"key":"41410_CR22","doi-asserted-by":"publisher","first-page":"20220193","DOI":"10.1098\/rspb.2022.0193","volume":"289","author":"HK Frank","year":"2022","unstructured":"Frank, H. K., Enard, D. & Boyd, S. D. Exceptional diversity and selection pressure on coronavirus host receptors in bats compared to other mammals. Proc. R. Soc. B Biol. Sci. 289, 20220193 (2022).","journal-title":"Proc. R. Soc. B Biol. Sci."},{"key":"41410_CR23","first-page":"202010146","volume":"30","author":"J Damas","year":"2020","unstructured":"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. U. S. A. 30, 202010146 (2020).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"41410_CR24","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00902-20","author":"H Guo","year":"2020","unstructured":"Guo, H. et al. Evolutionary arms race between virus and host drives genetic diversity in bat severe acute respiratory syndrome-related coronavirus spike genes. J. Virol. https:\/\/doi.org\/10.1128\/JVI.00902-20 (2020).","journal-title":"J. Virol."},{"key":"41410_CR25","doi-asserted-by":"publisher","first-page":"e1011116","DOI":"10.1371\/journal.ppat.1011116","volume":"19","author":"P Li","year":"2023","unstructured":"Li, P. et al. Effect of polymorphism in Rhinolophus affinis ACE2 on entry of SARS-CoV-2 related bat coronaviruses. PLoS Pathog. 19, e1011116 (2023).","journal-title":"PLoS Pathog."},{"key":"41410_CR26","doi-asserted-by":"publisher","first-page":"10915","DOI":"10.1073\/pnas.89.22.10915","volume":"89","author":"S Henikoff","year":"1992","unstructured":"Henikoff, S. & Henikoff, J. G. Amino acid substitution matrices from protein blocks. Proc. Natl. Acad. Sci. USA. 89, 10915\u201310919 (1992).","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"41410_CR27","doi-asserted-by":"publisher","first-page":"2001005","DOI":"10.2807\/1560-7917.ES.2020.25.23.2001005","volume":"25","author":"N Oreshkova","year":"2020","unstructured":"Oreshkova, N. et al. SARS-CoV-2 infection in farmed minks, the Netherlands, April and May 2020. Euro Surveill. 25, 2001005 (2020).","journal-title":"Euro Surveill."},{"key":"41410_CR28","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","volume":"579","author":"P Zhou","year":"2020","unstructured":"Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270\u2013273 (2020).","journal-title":"Nature"},{"key":"41410_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2021.01.011","author":"P Li","year":"2021","unstructured":"Li, P. et al. The Rhinolophus affinis bat ACE2 and multiple animal orthologs are functional receptors for bat coronavirus RaTG13 and SARS-CoV-2. Sci. Bull. https:\/\/doi.org\/10.1016\/j.scib.2021.01.011 (2021).","journal-title":"Sci. Bull."},{"key":"41410_CR30","doi-asserted-by":"publisher","first-page":"103643","DOI":"10.1016\/j.ebiom.2021.103643","volume":"73","author":"H Shuai","year":"2021","unstructured":"Shuai, H. et al. Emerging SARS-CoV-2 variants expand species tropism to murines. EBioMedicine 73, 103643 (2021).","journal-title":"EBioMedicine"},{"key":"41410_CR31","doi-asserted-by":"publisher","first-page":"4078","DOI":"10.1038\/s41467-023-39782-x","volume":"14","author":"A Feng","year":"2023","unstructured":"Feng, A. et al. Transmission of SARS-CoV-2 in free-ranging white-tailed deer in the United States. Nat. Commun. 14, 4078 (2023).","journal-title":"Nat. Commun."},{"key":"41410_CR32","doi-asserted-by":"publisher","first-page":"veab007","DOI":"10.1093\/ve\/veab007","volume":"7","author":"HL Wells","year":"2021","unstructured":"Wells, H. L. et al. The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus. Virus Evol. 7, veab007 (2021).","journal-title":"Virus Evol."},{"key":"41410_CR33","doi-asserted-by":"publisher","first-page":"e3002097","DOI":"10.1371\/journal.pbio.3002097","volume":"21","author":"MS Strine","year":"2023","unstructured":"Strine, M. S. et al. DYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner. PLoS Biol. 21, e3002097 (2023).","journal-title":"PLoS Biol."},{"key":"41410_CR34","doi-asserted-by":"publisher","first-page":"25057","DOI":"10.1073\/pnas.1912503116","volume":"116","author":"VA Avanzato","year":"2019","unstructured":"Avanzato, V. A. et al. A structural basis for antibody-mediated neutralization of Nipah virus reveals a site of vulnerability at the fusion glycoprotein apex. Proc. Natl. Acad. Sci. USA. 116, 25057\u201325067 (2019).","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"41410_CR35","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s13062-022-00325-x","volume":"17","author":"Y Zhu","year":"2022","unstructured":"Zhu, Y. et al. Long-range enhancement of N501Y-endowed mouse infectivity of SARS-CoV-2 by the non-RBD mutations of Ins215KLRS and H655Y. Biol. Direct. 17, 14 (2022).","journal-title":"Biol. Direct."},{"key":"41410_CR36","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/s41421-022-00431-0","volume":"8","author":"L Li","year":"2022","unstructured":"Li, L. et al. Broader-species receptor binding and structural bases of Omicron SARS-CoV-2 to both mouse and palm-civet ACE2s. Cell. Discov. 8, 65 (2022).","journal-title":"Cell. Discov."},{"key":"41410_CR37","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/nature02145","volume":"426","author":"W Li","year":"2003","unstructured":"Li, W. et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426, 450\u2013454 (2003).","journal-title":"Nature"},{"key":"41410_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04532-4","author":"S Temmam","year":"2022","unstructured":"Temmam, S. et al. Bat coronaviruses related to SARS-CoV-2 and infectious for human cells. Nature https:\/\/doi.org\/10.1038\/s41586-022-04532-4 (2022).","journal-title":"Nature"},{"key":"41410_CR39","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/s41586-020-2179-y","volume":"581","author":"J Shang","year":"2020","unstructured":"Shang, J. et al. Structural basis of receptor recognition by SARS-CoV-2. Nature 581, 221\u2013224 (2020).","journal-title":"Nature"},{"key":"41410_CR40","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/s41586-020-2180-5","volume":"581","author":"J Lan","year":"2020","unstructured":"Lan, J. et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature 581, 215\u2013220 (2020).","journal-title":"Nature"},{"key":"41410_CR41","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00990-23","author":"S Fujita","year":"2023","unstructured":"Fujita, S. et al. Determination of the factors responsible for the tropism of SARS-CoV-2-related bat coronaviruses to Rhinolophus bat ACE2. J. Virol. https:\/\/doi.org\/10.1128\/jvi.00990-23 (2023).","journal-title":"J. Virol."},{"key":"41410_CR42","unstructured":"ML, M. Interrater reliability: the kappa statistic - PMC. Biochemia Medica (2012). at https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC3900052\/"},{"key":"41410_CR43","doi-asserted-by":"publisher","first-page":"102545","DOI":"10.1016\/j.mex.2023.102545","volume":"12","author":"G Marzi","year":"2024","unstructured":"Marzi, G., Balzano, M. & Marchiori, D. K-Alpha calculator\u2013Krippendorff\u2019s alpha calculator: A user-friendly tool for computing Krippendorff\u2019s Alpha inter-rater reliability coefficient. MethodsX 12, 102545 (2024).","journal-title":"MethodsX"},{"key":"41410_CR44","doi-asserted-by":"publisher","DOI":"10.1101\/2022.05.16.492068","author":"N Mollentze","year":"2022","unstructured":"Mollentze, N., Keen, D., Munkhbayar, U., Biek, R. & Streicker, D. G. Variation in the ACE2 receptor has limited utility for SARS-CoV-2 host prediction. bioRxiv https:\/\/doi.org\/10.1101\/2022.05.16.492068 (2022).","journal-title":"bioRxiv"},{"key":"41410_CR45","doi-asserted-by":"publisher","DOI":"10.1101\/2020.12.07.414292","author":"G Du","year":"2020","unstructured":"Du, G. et al. A framework for predicting potential host ranges of pathogenic viruses based on receptor ortholog analysis. Biorxiv https:\/\/doi.org\/10.1101\/2020.12.07.414292 (2020).","journal-title":"Biorxiv"},{"key":"41410_CR46","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.coviro.2017.07.020","volume":"25","author":"A Sinha","year":"2017","unstructured":"Sinha, A. & Johnson, W. E. ScienceDirect Retroviruses of the RDR superinfection interference group: ancient origins and broad host distribution of a promiscuous Env gene. Curr. Opin. Virol. 25, 105\u2013112 (2017).","journal-title":"Curr. Opin. Virol."},{"key":"41410_CR47","doi-asserted-by":"publisher","first-page":"13087","DOI":"10.1073\/pnas.1814309115","volume":"115","author":"L Cao","year":"2018","unstructured":"Cao, L. et al. Seneca Valley virus attachment and uncoating mediated by its receptor anthrax toxin receptor 1. Proc. Natl. Acad. Sci. U. S. A. 115, 13087\u201313092 (2018).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"41410_CR48","doi-asserted-by":"publisher","first-page":"5105","DOI":"10.1038\/s41467-023-40706-y","volume":"14","author":"DS McBride","year":"2023","unstructured":"McBride, D. S. et al. Accelerated evolution of SARS-CoV-2 in free-ranging white-tailed deer. Nat. Commun. 14, 5105 (2023).","journal-title":"Nat. Commun."},{"key":"41410_CR49","doi-asserted-by":"publisher","first-page":"e1010197","DOI":"10.1371\/journal.ppat.1010197","volume":"18","author":"M Martins","year":"2022","unstructured":"Martins, M. et al. From deer-to-deer: SARS-CoV-2 is efficiently transmitted and presents broad tissue tropism and replication sites in white-tailed deer. PLoS Pathog. 18, e1010197 (2022).","journal-title":"PLoS Pathog."},{"key":"41410_CR50","doi-asserted-by":"publisher","first-page":"e2121644119","DOI":"10.1073\/pnas.2121644119","volume":"119","author":"SV Kuchipudi","year":"2022","unstructured":"Kuchipudi, S. V. et al. Multiple spillovers from humans and onward transmission of SARS-CoV-2 in white-tailed deer. Proc Nat. Acad. Sci. 119, e2121644119 (2022).","journal-title":"Proc Nat. Acad. Sci."},{"key":"41410_CR51","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/s41586-021-04353-x","volume":"602","author":"VL Hale","year":"2022","unstructured":"Hale, V. L. et al. SARS-CoV-2 infection in free-ranging white-tailed deer. Nature 602, 481\u2013486 (2022).","journal-title":"Nature"},{"key":"41410_CR52","doi-asserted-by":"publisher","first-page":"2988","DOI":"10.1038\/s41467-022-30698-6","volume":"13","author":"CCS Tan","year":"2022","unstructured":"Tan, C. C. S. et al. Transmission of SARS-CoV-2 from humans to animals and potential host adaptation. Nat. Commun. 13, 2988 (2022).","journal-title":"Nat. Commun."},{"key":"41410_CR53","doi-asserted-by":"publisher","first-page":"nwac122","DOI":"10.1093\/nsr\/nwac122","volume":"9","author":"S Li","year":"2022","unstructured":"Li, S. et al. Cross-species recognition and molecular basis of SARS-CoV-2 and SARS-CoV binding to ACE2s of marine animals. Natl. Sci. Rev. 9, nwac122 (2022).","journal-title":"Natl. Sci. Rev."},{"key":"41410_CR54","doi-asserted-by":"publisher","first-page":"143346","DOI":"10.1016\/j.scitotenv.2020.143346","volume":"760","author":"S Mathavarajah","year":"2021","unstructured":"Mathavarajah, S., Stoddart, A. K., Gagnon, G. A. & Dellaire, G. Pandemic danger to the deep: The risk of marine mammals contracting SARS-CoV-2 from wastewater. Sci. Total Environ. 760, 143346 (2021).","journal-title":"Sci. Total Environ."},{"key":"41410_CR55","doi-asserted-by":"publisher","first-page":"20230321","DOI":"10.1098\/rsbl.2023.0321","volume":"19","author":"HM Stone","year":"2023","unstructured":"Stone, H. M., Unal, E., Romano, T. A. & Turner, P. E. Beluga whale and bottlenose dolphin ACE2 proteins allow cell entry mediated by spike protein from three variants of SARS-CoV-2. Biol. Lett. 19, 20230321 (2023).","journal-title":"Biol. Lett."},{"key":"41410_CR56","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.3390\/ani11061663","volume":"11","author":"T Audino","year":"2021","unstructured":"Audino, T. et al. SARS-CoV-2, a threat to marine mammals? A study from Italian seawaters. Animals 11, 1663 (2021).","journal-title":"Animals"},{"key":"41410_CR57","doi-asserted-by":"publisher","unstructured":"Montagutelli, X. et al. The B1.351 and P.1 variants extend SARS-CoV-2 host range to mice. bioRxiv (2021). https:\/\/doi.org\/10.1101\/2021.03.18.436013","DOI":"10.1101\/2021.03.18.436013"},{"key":"41410_CR58","doi-asserted-by":"publisher","first-page":"840757","DOI":"10.3389\/fmicb.2022.840757","volume":"13","author":"F Tarr\u00e9s-Freixas","year":"2022","unstructured":"Tarr\u00e9s-Freixas, F. et al. Heterogeneous infectivity and pathogenesis of SARS-CoV-2 variants Beta, Delta and Omicron in transgenic K18-hACE2 and wildtype mice. Front. Microbiol. 13, 840757 (2022).","journal-title":"Front. Microbiol."},{"key":"41410_CR59","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1038\/nrmicro.2017.45","volume":"15","author":"RK Plowright","year":"2017","unstructured":"Plowright, R. K. et al. Pathways to zoonotic spillover. Nat. Rev. Microbiol. 15, 502\u2013510 (2017).","journal-title":"Nat. Rev. Microbiol."},{"key":"41410_CR60","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1638\/2020-0171","volume":"51","author":"SL Bartlett","year":"2021","unstructured":"Bartlett, S. L. et al. SARS-CoV-2 infection and longitudinal fecal screening in Malayan tigers (Panthera tigris jacksoni), Amur tigers (Panthera tigris altaica), and African lions (Panthera leo krugeri) at the Bronx Zoo, New York, USA. J. Zoo Wildl. Med. 51, 733\u2013744 (2021).","journal-title":"J. Zoo Wildl. Med."},{"key":"41410_CR61","doi-asserted-by":"publisher","first-page":"100164","DOI":"10.1016\/j.onehlt.2020.100164","volume":"10","author":"S Temmam","year":"2020","unstructured":"Temmam, S. et al. Absence of SARS-CoV-2 infection in cats and dogs in close contact with a cluster of COVID-19 patients in a veterinary campus. One Health 10, 100164 (2020).","journal-title":"One Health"},{"key":"41410_CR62","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1080\/22221751.2020.1817796","volume":"9","author":"Q Zhang","year":"2020","unstructured":"Zhang, Q. et al. A serological survey of SARS-CoV-2 in cat in Wuhan. Emerg. Microbes Infect. 9, 2013\u20132019 (2020).","journal-title":"Emerg. Microbes Infect."},{"key":"41410_CR63","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1007\/s11033-023-09099-5","volume":"51","author":"EA Fern\u00e1ndez-Figueroa","year":"2024","unstructured":"Fern\u00e1ndez-Figueroa, E. A. et al. Evidence of SARS-CoV-2 infection in companion animals from owners who tested positive for COVID-19 in the Valley of Mexico. Mol. Biol. Rep. 51, 186 (2024).","journal-title":"Mol. Biol. Rep."},{"key":"41410_CR64","doi-asserted-by":"publisher","first-page":"26382","DOI":"10.1073\/pnas.2013102117","volume":"117","author":"AM Bosco-Lauth","year":"2020","unstructured":"Bosco-Lauth, A. M. et al. Experimental infection of domestic dogs and cats with SARS-CoV-2: Pathogenesis, transmission, and response to reexposure in cats. Proc. Natl. Acad. Sci. 117, 26382\u201326388 (2020).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"41410_CR65","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1093\/bioinformatics\/btp033","volume":"25","author":"AM Waterhouse","year":"2009","unstructured":"Waterhouse, A. M., Procter, J. B., Martin, D. M. A., Clamp, M. & Barton, G. J. Jalview Version 2--a multiple sequence alignment editor and analysis workbench. Bioinformatics 25, 1189\u20131191 (2009).","journal-title":"Bioinformatics"},{"key":"41410_CR66","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1093\/nar\/gkg033","volume":"31","author":"DL Wheeler","year":"2003","unstructured":"Wheeler, D. L. Database resources of the National Center for Biotechnology. Nucleic Acids Res. 31, 28\u201333 (2003).","journal-title":"Nucleic Acids Res."},{"key":"41410_CR67","doi-asserted-by":"publisher","first-page":"D733","DOI":"10.1093\/nar\/gkv1189","volume":"44","author":"NA O\u2019Leary","year":"2016","unstructured":"O\u2019Leary, N. A. et al. Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. Nucl. Acids Res. 44, D733\u2013D745 (2016).","journal-title":"Nucl. Acids Res."},{"key":"41410_CR68","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1093\/bioinformatics\/btp163","volume":"25","author":"PJA Cock","year":"2009","unstructured":"Cock, P. J. A. et al. Biopython: Freely available Python tools for computational molecular biology and bioinformatics. Bioinformatics 25, 1422\u20131423 (2009).","journal-title":"Bioinformatics"},{"key":"41410_CR69","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/S0168-9525(00)02024-2","volume":"16","author":"P Rice","year":"2000","unstructured":"Rice, P., Longden, I. & Bleasby, A. EMBOSS: The European molecular biology open software suite. Trends Genet. 16, 276\u2013277 (2000).","journal-title":"Trends Genet."},{"key":"41410_CR70","doi-asserted-by":"publisher","first-page":"3059","DOI":"10.1093\/nar\/gkf436","volume":"30","author":"K Katoh","year":"2002","unstructured":"Katoh, K., Misawa, K., Kuma, K. & Miyata, T. MAFFT: A novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res. 30, 3059\u20133066 (2002).","journal-title":"Nucleic Acids Res."},{"key":"41410_CR71","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1093\/nar\/gkh340","volume":"32","author":"RC Edgar","year":"2004","unstructured":"Edgar, R. C. MUSCLE: Multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32, 1792\u20131797 (2004).","journal-title":"Nucleic Acids Res."},{"key":"41410_CR72","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.21105\/joss.01686","volume":"4","author":"H Wickham","year":"2019","unstructured":"Wickham, H. et al. Welcome to the Tidyverse. J. Open Source Softw. 4, 1686 (2019).","journal-title":"J. Open Source Softw."},{"key":"41410_CR73","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1126\/science.1116480","volume":"309","author":"F Li","year":"2005","unstructured":"Li, F., Li, W., Farzan, M. & Harrison, S. C. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science 309, 1864\u20131868 (2005).","journal-title":"Science"},{"key":"41410_CR74","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/pro.3943","volume":"30","author":"EF Pettersen","year":"2021","unstructured":"Pettersen, E. F. et al. UCSF ChimeraX: Structure visualization for researchers, educators, and developers. Protein Sci. 30, 70\u201382 (2021).","journal-title":"Protein Sci."},{"key":"41410_CR75","doi-asserted-by":"publisher","first-page":"e1010828","DOI":"10.1371\/journal.ppat.1010828","volume":"18","author":"SN Seifert","year":"2022","unstructured":"Seifert, S. N. et al. An ACE2-dependent sarbecovirus in Russian bats is resistant to SARS-CoV-2 vaccines. PLoS Pathog. 18, e1010828 (2022).","journal-title":"PLoS Pathog."},{"key":"41410_CR76","doi-asserted-by":"publisher","first-page":"msab327","DOI":"10.1093\/molbev\/msab327","volume":"39","author":"YA Chan","year":"2021","unstructured":"Chan, Y. A. & Zhan, S. H. The emergence of the spike furin cleavage site in SARS-CoV-2. Mol. Biol. Evol. 39, msab327 (2021).","journal-title":"Mol. Biol. Evol."},{"key":"41410_CR77","doi-asserted-by":"publisher","first-page":"e5179","DOI":"10.7717\/peerj.5179","volume":"6","author":"SR Borstein","year":"2018","unstructured":"Borstein, S. R. & O\u2019Meara, B. C. AnnotationBustR: An R package to extract subsequences from GenBank annotations. PeerJ 6, e5179 (2018).","journal-title":"PeerJ"},{"key":"41410_CR78","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1093\/molbev\/msu300","volume":"32","author":"L-T Nguyen","year":"2015","unstructured":"Nguyen, L.-T., Schmidt, H. A., von Haeseler, A. & Minh, B. Q. IQ-TREE: A fast and effective stochastic algorithm for estimating Maximum-Likelihood phylogenies. Mol. Biol. Evol. 32, 268\u2013274 (2015).","journal-title":"Mol. Biol. Evol."},{"key":"41410_CR79","doi-asserted-by":"publisher","first-page":"706907","DOI":"10.3389\/fgene.2021.706907","volume":"12","author":"C-H Gao","year":"2021","unstructured":"Gao, C.-H., Yu, G. & Cai, P. ggVennDiagram: An intuitive, easy-to-use, and highly customizable R package to generate Venn Diagram. Front. Genet. 12, 706907 (2021).","journal-title":"Front. Genet."},{"key":"41410_CR80","unstructured":"Lenth, R. V. & Piaskowski, J. emmeans: Estimated Marginal Means, aka Least-Squares Means. R package version 2.0.0. at https:\/\/rvlenth.github.io\/emmeans\/"},{"key":"41410_CR81","doi-asserted-by":"publisher","unstructured":"Meyer, D., Zeileis, A., Hornik, K., Gerber, F. & Friendly, M. vcd: Visualizing Categorical Data. https:\/\/doi.org\/10.32614\/cran.package.vcd (2024)","DOI":"10.32614\/cran.package.vcd"},{"issue":"1","key":"41410_CR82","doi-asserted-by":"publisher","first-page":"27","DOI":"10.32614\/cran.package.irr","volume":"26","author":"L Stadtmann","year":"2025","unstructured":"Stadtmann, L. et al. Changes in patient-reported chief complaints with orthognathic surgery: a prospective cohort study. Progress Orthodont. 26(1), 27. https:\/\/doi.org\/10.32614\/cran.package.irr (2025).","journal-title":"Progress Orthodont."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-41410-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-41410-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-41410-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T10:01:36Z","timestamp":1777629696000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-41410-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":82,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["41410"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-41410-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]},"assertion":[{"value":"16 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This work was supported by the Howard Hughes Medical Institute (A.I.). J.A.F. is a Cancer Research Institute Irvington Fellow supported by the Cancer Research Institute (CRI4017). None of the authors have a conflict of interest to report.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"13995"}}