{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T01:11:08Z","timestamp":1780449068336,"version":"3.54.1"},"reference-count":86,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T00:00:00Z","timestamp":1667520000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T00:00:00Z","timestamp":1667520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People\u2019s Republic of China","doi-asserted-by":"publisher","award":["2018ZX10731-101-001-010"],"award-info":[{"award-number":["2018ZX10731-101-001-010"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070170"],"award-info":[{"award-number":["32070170"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82041036"],"award-info":[{"award-number":["82041036"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Understanding the antigenic signatures of all human coronaviruses (HCoVs) Spike (S) proteins is imperative for pan-HCoV epitopes identification and broadly effective vaccine development. To depict the currently elusive antigenic signatures of \u03b1-HCoVs S proteins, we isolated a panel of antibodies against the HCoV-229E S protein and characterized their epitopes and neutralizing potential. We found that the N-terminal domain of HCoV-229E S protein is antigenically dominant wherein an antigenic supersite is present and appears conserved in HCoV-NL63, which holds potential to serve as a pan-\u03b1-HCoVs epitope. In the receptor binding domain, a neutralizing epitope is captured in the end distal to the receptor binding site, reminiscent of the locations of the SARS-CoV-2 RBD cryptic epitopes. We also identified a neutralizing antibody that recognizes the connector domain, thus representing the first S2-directed neutralizing antibody against \u03b1-HCoVs. The unraveled HCoVs S proteins antigenic similarities and variances among genera highlight the challenges faced by pan-HCoV vaccine design while supporting the feasibility of broadly effective vaccine development against a subset of HCoVs.<\/jats:p>","DOI":"10.1038\/s42003-022-04160-8","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T16:04:58Z","timestamp":1667577898000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Antigenic mapping reveals sites of vulnerability on \u03b1-HCoV spike protein"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9918-4967","authenticated-orcid":false,"given":"Jiangchao","family":"Xiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoshuai","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8069-7511","authenticated-orcid":false,"given":"Youwei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilian","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7755-5918","authenticated-orcid":false,"given":"Sachdev","family":"Sidhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2255-0391","authenticated-orcid":false,"given":"Lu","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4785-4508","authenticated-orcid":false,"given":"Shane","family":"Miersch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5389-3859","authenticated-orcid":false,"given":"Bei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,4]]},"reference":[{"key":"4160_CR1","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/s41579-018-0118-9","volume":"17","author":"J Cui","year":"2019","unstructured":"Cui, J., Li, F. & Shi, Z. L. Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbiol. 17, 181\u2013192 (2019).","journal-title":"Nat. Rev. Microbiol."},{"key":"4160_CR2","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1146\/annurev-micro-020518-115759","volume":"73","author":"TS Fung","year":"2019","unstructured":"Fung, T. S. & Liu, D. X. Human Coronavirus: Host-Pathogen Interaction. Annu Rev. Microbiol. 73, 529\u2013557 (2019).","journal-title":"Annu Rev. Microbiol."},{"key":"4160_CR3","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1016\/j.mayocp.2020.05.032","volume":"95","author":"SL Rucinski","year":"2020","unstructured":"Rucinski, S. L., Binnicker, M. J., Thomas, A. S. & Patel, R. Seasonality of Coronavirus 229E, HKU1, NL63, and OC43 From 2014 to 2020. Mayo Clin. Proc. 95, 1701\u20131703 (2020).","journal-title":"Mayo Clin. Proc."},{"key":"4160_CR4","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1126\/science.372.6539.227","volume":"372","author":"J Cohen","year":"2021","unstructured":"Cohen, J. The dream vaccine. Science 372, 227\u2013231 (2021).","journal-title":"Science"},{"key":"4160_CR5","doi-asserted-by":"publisher","first-page":"100721","DOI":"10.1016\/j.drup.2020.100721","volume":"53","author":"A Artese","year":"2020","unstructured":"Artese, A. et al. Current status of antivirals and druggable targets of SARS CoV-2 and other human pathogenic coronaviruses. Drug Resist. Updat. 53, 100721 (2020).","journal-title":"Drug Resist. Updat."},{"key":"4160_CR6","doi-asserted-by":"publisher","first-page":"e1005815","DOI":"10.1371\/journal.ppat.1005815","volume":"12","author":"JG Jardine","year":"2016","unstructured":"Jardine, J. G. et al. Minimally Mutated HIV-1 Broadly Neutralizing Antibodies to Guide Reductionist Vaccine Design. PLoS Pathog. 12, e1005815 (2016).","journal-title":"PLoS Pathog."},{"key":"4160_CR7","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.virol.2015.03.043","volume":"479-480","author":"SC Harrison","year":"2015","unstructured":"Harrison, S. C. Viral membrane fusion. Virology 479-480, 498\u2013507 (2015).","journal-title":"Virology"},{"key":"4160_CR8","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.coviro.2013.03.006","volume":"3","author":"E Baquero","year":"2013","unstructured":"Baquero, E. et al. Intermediate conformations during viral fusion glycoprotein structural transition. Curr. Opin. Virol. 3, 143\u2013150 (2013).","journal-title":"Curr. Opin. Virol."},{"key":"4160_CR9","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1038\/nsmb.3293","volume":"23","author":"AC Walls","year":"2016","unstructured":"Walls, A. C. et al. Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy. Nat. Struct. Mol. Biol. 23, 899\u2013905 (2016).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"4160_CR10","doi-asserted-by":"publisher","unstructured":"Li, Z. et al. The human coronavirus HCoV-229E S-protein structure and receptor binding. Elife 8, https:\/\/doi.org\/10.7554\/eLife.51230 (2019).","DOI":"10.7554\/eLife.51230"},{"key":"4160_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20401-y","volume":"12","author":"X Song","year":"2021","unstructured":"Song, X. et al. Cryo-EM analysis of the HCoV-229E spike glycoprotein reveals dynamic prefusion conformational changes. Nat. Commun. 12, 141 (2021).","journal-title":"Nat. Commun."},{"key":"4160_CR12","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/cr.2016.152","volume":"27","author":"M Gui","year":"2017","unstructured":"Gui, M. et al. Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding. Cell Res. 27, 119\u2013129 (2017).","journal-title":"Cell Res."},{"key":"4160_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15092","volume":"8","author":"Y Yuan","year":"2017","unstructured":"Yuan, Y. et al. Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains. Nat. Commun. 8, 15092 (2017).","journal-title":"Nat. Commun."},{"key":"4160_CR14","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","volume":"181","author":"AC Walls","year":"2020","unstructured":"Walls, A. C. et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181, 281\u2013292.e286 (2020).","journal-title":"Cell"},{"key":"4160_CR15","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1126\/science.abb2507","volume":"367","author":"D Wrapp","year":"2020","unstructured":"Wrapp, D. et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367, 1260\u20131263 (2020).","journal-title":"Science"},{"key":"4160_CR16","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/nrd.2015.37","volume":"15","author":"A Zumla","year":"2016","unstructured":"Zumla, A., Chan, J. F., Azhar, E. I., Hui, D. S. & Yuen, K. Y. Coronaviruses\u2014drug discovery and therapeutic options. Nat. Rev. Drug Disco. 15, 327\u2013347 (2016).","journal-title":"Nat. Rev. Drug Disco."},{"key":"4160_CR17","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1038\/s41577-021-00542-x","volume":"21","author":"PC Taylor","year":"2021","unstructured":"Taylor, P. C. et al. Neutralizing monoclonal antibodies for treatment of COVID-19. Nat. Rev. Immunol. 21, 382\u2013393 (2021).","journal-title":"Nat. Rev. Immunol."},{"key":"4160_CR18","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1002\/rmv.706","volume":"22","author":"MM Coughlin","year":"2012","unstructured":"Coughlin, M. M. & Prabhakar, B. S. Neutralizing human monoclonal antibodies to severe acute respiratory syndrome coronavirus: target, mechanism of action, and therapeutic potential. Rev. Med Virol. 22, 2\u201317 (2012).","journal-title":"Rev. Med Virol."},{"key":"4160_CR19","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/s41579-021-00573-0","volume":"19","author":"WT Harvey","year":"2021","unstructured":"Harvey, W. T. et al. SARS-CoV-2 variants, spike mutations and immune escape. Nat. Rev. Microbiol 19, 409\u2013424 (2021).","journal-title":"Nat. Rev. Microbiol"},{"key":"4160_CR20","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1016\/j.cell.2020.09.037","volume":"183","author":"L Piccoli","year":"2020","unstructured":"Piccoli, L. et al. Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology. Cell 183, 1024\u20131042.e1021 (2020).","journal-title":"Cell"},{"key":"4160_CR21","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1016\/j.it.2020.09.004","volume":"41","author":"E Gavor","year":"2020","unstructured":"Gavor, E., Choong, Y. K., Er, S. Y., Sivaraman, H. & Sivaraman, J. Structural basis of SARS-CoV-2 and SARS-CoV antibody interactions. Trends Immunol. 41, 1006\u20131022 (2020).","journal-title":"Trends Immunol."},{"key":"4160_CR22","doi-asserted-by":"publisher","first-page":"3395","DOI":"10.1016\/j.celrep.2019.08.052","volume":"28","author":"N Wang","year":"2019","unstructured":"Wang, N. et al. Structural definition of a neutralization-sensitive epitope on the MERS-CoV S1-NTD. Cell Rep. 28, 3395\u20133405.e3396 (2019).","journal-title":"Cell Rep."},{"key":"4160_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10897-4","volume":"10","author":"H Zhou","year":"2019","unstructured":"Zhou, H. et al. Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein. Nat. Commun. 10, 3068 (2019).","journal-title":"Nat. Commun."},{"key":"4160_CR24","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1126\/science.abc6952","volume":"369","author":"X Chi","year":"2020","unstructured":"Chi, X. et al. A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science 369, 650\u2013655 (2020).","journal-title":"Science"},{"key":"4160_CR25","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.chom.2021.03.005","volume":"29","author":"G Cerutti","year":"2021","unstructured":"Cerutti, G. et al. Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite. Cell Host Microbe 29, 819\u2013833 e817 (2021).","journal-title":"Cell Host Microbe"},{"key":"4160_CR26","doi-asserted-by":"publisher","unstructured":"McCallum, M. et al. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell, https:\/\/doi.org\/10.1016\/j.cell.2021.03.028 (2021).","DOI":"10.1016\/j.cell.2021.03.028"},{"key":"4160_CR27","doi-asserted-by":"publisher","unstructured":"Suryadevara, N. et al. Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein. Cell, https:\/\/doi.org\/10.1016\/j.cell.2021.03.029 (2021).","DOI":"10.1016\/j.cell.2021.03.029"},{"key":"4160_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30658-0","volume":"13","author":"C Wang","year":"2022","unstructured":"Wang, C. et al. Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes. Nat. Commun. 13, 2921 (2022).","journal-title":"Nat. Commun."},{"key":"4160_CR29","doi-asserted-by":"publisher","first-page":"eabn2911","DOI":"10.1126\/sciadv.abn2911","volume":"8","author":"S Bangaru","year":"2022","unstructured":"Bangaru, S. et al. Structural mapping of antibody landscapes to human betacoronavirus spike proteins. Sci. Adv. 8, eabn2911 (2022).","journal-title":"Sci. Adv."},{"key":"4160_CR30","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/nrmicro2090","volume":"7","author":"L Du","year":"2009","unstructured":"Du, L. et al. The spike protein of SARS-CoV\u2013a target for vaccine and therapeutic development. Nat. Rev. Microbiol 7, 226\u2013236 (2009).","journal-title":"Nat. Rev. Microbiol"},{"key":"4160_CR31","doi-asserted-by":"publisher","unstructured":"Shi, W. et al. Vaccine-elicited murine antibody WS6 neutralizes diverse beta-coronaviruses by recognizing a helical stem supersite of vulnerability. Structure, https:\/\/doi.org\/10.1016\/j.str.2022.06.004 (2022).","DOI":"10.1016\/j.str.2022.06.004"},{"key":"4160_CR32","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1038\/s42003-022-03262-7","volume":"5","author":"NK Hurlburt","year":"2022","unstructured":"Hurlburt, N. K. et al. Structural definition of a pan-sarbecovirus neutralizing epitope on the spike S2 subunit. Commun. Biol. 5, 342 (2022).","journal-title":"Commun. Biol."},{"key":"4160_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21968-w","volume":"12","author":"C Wang","year":"2021","unstructured":"Wang, C. et al. A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies. Nat. Commun. 12, 1715 (2021).","journal-title":"Nat. Commun."},{"key":"4160_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23074-3","volume":"12","author":"G Song","year":"2021","unstructured":"Song, G. et al. Cross-reactive serum and memory B-cell responses to spike protein in SARS-CoV-2 and endemic coronavirus infection. Nat. Commun. 12, 2938 (2021).","journal-title":"Nat. Commun."},{"key":"4160_CR35","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1038\/s41594-021-00596-4","volume":"28","author":"MM Sauer","year":"2021","unstructured":"Sauer, M. M. et al. Structural basis for broad coronavirus neutralization. Nat. Struct. Mol. Biol. 28, 478\u2013486 (2021).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"4160_CR36","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1126\/science.abj3321","volume":"373","author":"D Pinto","year":"2021","unstructured":"Pinto, D. et al. Broad betacoronavirus neutralization by a stem helix-specific human antibody. Science 373, 1109\u20131116 (2021).","journal-title":"Science"},{"key":"4160_CR37","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1128\/JVI.80.2.941-950.2006","volume":"80","author":"KM Lip","year":"2006","unstructured":"Lip, K. M. et al. Monoclonal antibodies targeting the HR2 domain and the region immediately upstream of the HR2 of the S protein neutralize in vitro infection of severe acute respiratory syndrome coronavirus. J. Virol. 80, 941\u2013950 (2006).","journal-title":"J. Virol."},{"key":"4160_CR38","doi-asserted-by":"publisher","first-page":"E7348","DOI":"10.1073\/pnas.1707304114","volume":"114","author":"J Pallesen","year":"2017","unstructured":"Pallesen, J. et al. Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. Proc. Natl Acad. Sci. USA 114, E7348\u2013E7357 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"4160_CR39","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1007\/s00216-010-3556-4","volume":"397","author":"SR Marcsisin","year":"2010","unstructured":"Marcsisin, S. R. & Engen, J. R. Hydrogen exchange mass spectrometry: what is it and what can it tell us. Anal. Bioanal. Chem. 397, 967\u2013972 (2010).","journal-title":"Anal. Bioanal. Chem."},{"key":"4160_CR40","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/j.jmb.2012.11.037","volume":"425","author":"H Persson","year":"2013","unstructured":"Persson, H. et al. CDR-H3 diversity is not required for antigen recognition by synthetic antibodies. J. Mol. Biol. 425, 803\u2013811 (2013).","journal-title":"J. Mol. Biol."},{"key":"4160_CR41","doi-asserted-by":"publisher","unstructured":"Tao, Y. et al. Tailored tetravalent antibodies potently and specifically activate Wnt\/Frizzled pathways in cells, organoids and mice. Elife 8, https:\/\/doi.org\/10.7554\/eLife.46134 (2019).","DOI":"10.7554\/eLife.46134"},{"key":"4160_CR42","doi-asserted-by":"publisher","first-page":"1717265","DOI":"10.1080\/19420862.2020.1717265","volume":"12","author":"E Gallo","year":"2020","unstructured":"Gallo, E. et al. In situ antibody phage display yields optimal inhibitors of integrin alpha11\/beta1. MAbs 12, 1717265 (2020).","journal-title":"MAbs"},{"key":"4160_CR43","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1016\/j.jmb.2020.01.012","volume":"432","author":"S Liu","year":"2020","unstructured":"Liu, S. et al. A synthetic human antibody antagonizes IL-18Rbeta signaling through an allosteric mechanism. J. Mol. Biol. 432, 1169\u20131182 (2020).","journal-title":"J. Mol. Biol."},{"key":"4160_CR44","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/357420a0","volume":"357","author":"CL Yeager","year":"1992","unstructured":"Yeager, C. L. et al. Human aminopeptidase N is a receptor for human coronavirus 229E. Nature 357, 420\u2013422 (1992).","journal-title":"Nature"},{"key":"4160_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01706-x","volume":"8","author":"AHM Wong","year":"2017","unstructured":"Wong, A. H. M. et al. Receptor-binding loops in alphacoronavirus adaptation and evolution. Nat. Commun. 8, 1735 (2017).","journal-title":"Nat. Commun."},{"key":"4160_CR46","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1146\/annurev-immunol-032712-095916","volume":"31","author":"D Corti","year":"2013","unstructured":"Corti, D. & Lanzavecchia, A. Broadly neutralizing antiviral antibodies. Annu Rev. Immunol. 31, 705\u2013742 (2013).","journal-title":"Annu Rev. Immunol."},{"key":"4160_CR47","doi-asserted-by":"publisher","first-page":"3086","DOI":"10.1016\/j.cell.2021.05.005","volume":"184","author":"D Corti","year":"2021","unstructured":"Corti, D., Purcell, L. A., Snell, G. & Veesler, D. Tackling COVID-19 with neutralizing monoclonal antibodies. Cell 184, 3086\u20133108 (2021).","journal-title":"Cell"},{"key":"4160_CR48","doi-asserted-by":"publisher","unstructured":"Zheng, Z. et al. Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2. Euro Surveill 25, https:\/\/doi.org\/10.2807\/1560-7917.ES.2020.25.28.2000291 (2020).","DOI":"10.2807\/1560-7917.ES.2020.25.28.2000291"},{"key":"4160_CR49","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1016\/j.cell.2021.02.035","volume":"184","author":"E Andreano","year":"2021","unstructured":"Andreano, E. et al. Extremely potent human monoclonal antibodies from COVID-19 convalescent patients. Cell 184, 1821\u20131835.e1816 (2021).","journal-title":"Cell"},{"key":"4160_CR50","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1016\/j.cell.2021.02.032","volume":"184","author":"W Dejnirattisai","year":"2021","unstructured":"Dejnirattisai, W. et al. The antigenic anatomy of SARS-CoV-2 receptor binding domain. Cell 184, 2183\u20132200.e2122 (2021).","journal-title":"Cell"},{"key":"4160_CR51","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1126\/science.abb7269","volume":"368","author":"M Yuan","year":"2020","unstructured":"Yuan, M. et al. A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV. Science 368, 630\u2013633 (2020).","journal-title":"Science"},{"key":"4160_CR52","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1038\/s41594-020-0480-y","volume":"27","author":"D Zhou","year":"2020","unstructured":"Zhou, D. et al. Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient. Nat. Struct. Mol. Biol. 27, 950\u2013958 (2020).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"4160_CR53","doi-asserted-by":"crossref","unstructured":"Zhan, W. et al. Structural study of SARS-CoV-2 antibodies identifies a broad-spectrum antibody that neutralizes the omicron variant by disassembling the spike trimer. J. Virol, e0048022, (2022).","DOI":"10.1128\/jvi.00480-22"},{"key":"4160_CR54","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/j.chom.2020.06.010","volume":"28","author":"J Huo","year":"2020","unstructured":"Huo, J. et al. Neutralization of SARS-CoV-2 by destruction of the prefusion spike. Cell Host Microbe 28, 445\u2013454 e446 (2020).","journal-title":"Cell Host Microbe"},{"key":"4160_CR55","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19146-5","volume":"11","author":"AG Wrobel","year":"2020","unstructured":"Wrobel, A. G. et al. Antibody-mediated disruption of the SARS-CoV-2 spike glycoprotein. Nat. Commun. 11, 5337 (2020).","journal-title":"Nat. Commun."},{"key":"4160_CR56","doi-asserted-by":"publisher","first-page":"e1009089","DOI":"10.1371\/journal.ppat.1009089","volume":"16","author":"NC Wu","year":"2020","unstructured":"Wu, N. C. et al. A natural mutation between SARS-CoV-2 and SARS-CoV determines neutralization by a cross-reactive antibody. PLoS Pathog. 16, e1009089 (2020).","journal-title":"PLoS Pathog."},{"key":"4160_CR57","doi-asserted-by":"publisher","unstructured":"Shi, Y. et al. Insight into vaccine development for Alpha-coronaviruses based on structural and immunological analyses of spike proteins. J. Virol., https:\/\/doi.org\/10.1128\/JVI.02284-20 (2021).","DOI":"10.1128\/JVI.02284-20"},{"key":"4160_CR58","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1038\/s41564-022-01155-3","volume":"7","author":"X Sun","year":"2022","unstructured":"Sun, X. et al. Neutralization mechanism of a human antibody with pan-coronavirus reactivity including SARS-CoV-2. Nat. Microbiol 7, 1063\u20131074 (2022).","journal-title":"Nat. Microbiol"},{"key":"4160_CR59","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1126\/science.abq3773","volume":"377","author":"C Dacon","year":"2022","unstructured":"Dacon, C. et al. Broadly neutralizing antibodies target the coronavirus fusion peptide. Science 377, 728\u2013735 (2022).","journal-title":"Science"},{"key":"4160_CR60","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1126\/science.abq2679","volume":"377","author":"JS Low","year":"2022","unstructured":"Low, J. S. et al. ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies. Science 377, 735\u2013742 (2022).","journal-title":"Science"},{"key":"4160_CR61","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.coi.2020.03.013","volume":"65","author":"AB Ward","year":"2020","unstructured":"Ward, A. B. & Wilson, I. A. Innovations in structure-based antigen design and immune monitoring for next generation vaccines. Curr. Opin. Immunol. 65, 50\u201356 (2020).","journal-title":"Curr. Opin. Immunol."},{"key":"4160_CR62","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1016\/j.jmb.2008.01.093","volume":"377","author":"S Birtalan","year":"2008","unstructured":"Birtalan, S. et al. The intrinsic contributions of tyrosine, serine, glycine and arginine to the affinity and specificity of antibodies. J. Mol. Biol. 377, 1518\u20131528 (2008).","journal-title":"J. Mol. Biol."},{"key":"4160_CR63","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1073\/pnas.82.2.488","volume":"82","author":"TA Kunkel","year":"1985","unstructured":"Kunkel, T. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc. Natl Acad. Sci. USA 82, 488\u2013492 (1985).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"4160_CR64","unstructured":"Fellouse, F. A. & Sidhu, S. S. In Making and Using Antibodies (eds Howard, G. C. & Kaser, M. R.) (CRC Press, 2006)."},{"key":"4160_CR65","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/s41392-021-00712-2","volume":"6","author":"S Xia","year":"2021","unstructured":"Xia, S. et al. Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation. Signal Transduct. Target Ther. 6, 288 (2021).","journal-title":"Signal Transduct. Target Ther."},{"key":"4160_CR66","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/s41422-020-0305-x","volume":"30","author":"S Xia","year":"2020","unstructured":"Xia, S. et al. Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Res. 30, 343\u2013355 (2020).","journal-title":"Cell Res."},{"key":"4160_CR67","doi-asserted-by":"publisher","first-page":"13499","DOI":"10.1073\/pnas.1918844117","volume":"117","author":"B Meng","year":"2020","unstructured":"Meng, B. et al. Inhibitory antibodies identify unique sites of therapeutic vulnerability in rhinovirus and other enteroviruses. Proc. Natl Acad. Sci. USA 117, 13499\u201313508 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"4160_CR68","doi-asserted-by":"publisher","first-page":"W252","DOI":"10.1093\/nar\/gku340","volume":"42","author":"M Biasini","year":"2014","unstructured":"Biasini, M. et al. SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res. 42, W252\u2013W258 (2014).","journal-title":"Nucleic Acids Res."},{"key":"4160_CR69","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","volume":"25","author":"EF Pettersen","year":"2004","unstructured":"Pettersen, E. F. et al. UCSF Chimera\u2014a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605\u20131612 (2004).","journal-title":"J. Comput. Chem."},{"key":"4160_CR70","doi-asserted-by":"publisher","first-page":"W363","DOI":"10.1093\/nar\/gki481","volume":"33","author":"D Schneidman-Duhovny","year":"2005","unstructured":"Schneidman-Duhovny, D., Inbar, Y., Nussinov, R. & Wolfson, H. J. PatchDock and SymmDock: servers for rigid and symmetric docking. Nucleic Acids Res. 33, W363\u2013W367 (2005).","journal-title":"Nucleic Acids Res."},{"key":"4160_CR71","doi-asserted-by":"publisher","first-page":"W229","DOI":"10.1093\/nar\/gkn186","volume":"36","author":"E Mashiach","year":"2008","unstructured":"Mashiach, E., Schneidman-Duhovny, D., Andrusier, N., Nussinov, R. & Wolfson, H. J. FireDock: a web server for fast interaction refinement in molecular docking. Nucleic Acids Res. 36, W229\u2013W232 (2008).","journal-title":"Nucleic Acids Res."},{"key":"4160_CR72","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/S0076-6879(97)76066-X","volume":"276","author":"Z Otwinowski","year":"1997","unstructured":"Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307\u2013326 (1997).","journal-title":"Methods Enzymol."},{"key":"4160_CR73","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1107\/S0021889809045701","volume":"43","author":"G Winter","year":"2009","unstructured":"Winter, G. xia2: an expert system for macromolecular crystallography data reduction. J. Appl. Crystallogr. 43, 186\u2013190 (2009).","journal-title":"J. Appl. Crystallogr."},{"key":"4160_CR74","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1107\/S0907444906045975","volume":"63","author":"AJ McCoy","year":"2007","unstructured":"McCoy, A. J. Solving structures of protein complexes by molecular replacement with Phaser. Acta Crystallogr. D: Biol. Crystallogr. 63, 32\u201341 (2007).","journal-title":"Acta Crystallogr. D: Biol. Crystallogr."},{"key":"4160_CR75","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1107\/S0907444904019158","volume":"60","author":"P Emsley","year":"2004","unstructured":"Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr D: Biol. Crystallogr. 60, 2126\u20132132 (2004).","journal-title":"Acta Crystallogr D: Biol. Crystallogr."},{"key":"4160_CR76","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1107\/S0907444909052925","volume":"66","author":"PD Adams","year":"2010","unstructured":"Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D: Biol. Crystallogr. 66, 213\u2013221 (2010).","journal-title":"Acta Crystallogr. D: Biol. Crystallogr."},{"key":"4160_CR77","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1107\/S0907444909042073","volume":"66","author":"VB Chen","year":"2010","unstructured":"Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr D: Biol. Crystallogr. 66, 12\u201321 (2010).","journal-title":"Acta Crystallogr D: Biol. Crystallogr."},{"key":"4160_CR78","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/j.jmb.2007.05.022","volume":"372","author":"E Krissinel","year":"2007","unstructured":"Krissinel, E. & Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774\u2013797 (2007).","journal-title":"J. Mol. Biol."},{"key":"4160_CR79","doi-asserted-by":"publisher","unstructured":"Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. Elife 7, https:\/\/doi.org\/10.7554\/eLife.42166 (2018).","DOI":"10.7554\/eLife.42166"},{"key":"4160_CR80","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jsb.2006.05.009","volume":"157","author":"G Tang","year":"2007","unstructured":"Tang, G. et al. EMAN2: an extensible image processing suite for electron microscopy. J. Struct. Biol. 157, 38\u201346 (2007).","journal-title":"J. Struct. Biol."},{"key":"4160_CR81","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/nmeth.4193","volume":"14","author":"SQ Zheng","year":"2017","unstructured":"Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331\u2013332 (2017).","journal-title":"Nat. Methods"},{"key":"4160_CR82","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.jsb.2015.08.008","volume":"192","author":"A Rohou","year":"2015","unstructured":"Rohou, A. & Grigorieff, N. CTFFIND4: Fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216\u2013221 (2015).","journal-title":"J. Struct. Biol."},{"key":"4160_CR83","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nmeth.4169","volume":"14","author":"A Punjani","year":"2017","unstructured":"Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290\u2013296 (2017).","journal-title":"Nat. Methods"},{"key":"4160_CR84","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1038\/msb.2011.75","volume":"7","author":"F Sievers","year":"2011","unstructured":"Sievers, F. et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7, 539 (2011).","journal-title":"Mol. Syst. Biol."},{"key":"4160_CR85","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1101\/gr.849004","volume":"14","author":"GE Crooks","year":"2004","unstructured":"Crooks, G. E., Hon, G., Chandonia, J. M. & Brenner, S. E. WebLogo: a sequence logo generator. Genome Res. 14, 1188\u20131190 (2004).","journal-title":"Genome Res."},{"key":"4160_CR86","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1093\/bioinformatics\/bth070","volume":"20","author":"C Berezin","year":"2004","unstructured":"Berezin, C. et al. ConSeq: the identification of functionally and structurally important residues in protein sequences. Bioinformatics 20, 1322\u20131324 (2004).","journal-title":"Bioinformatics"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-04160-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-04160-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-04160-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,6]],"date-time":"2022-11-06T10:02:55Z","timestamp":1667728975000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-04160-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,4]]},"references-count":86,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["4160"],"URL":"https:\/\/doi.org\/10.1038\/s42003-022-04160-8","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,4]]},"assertion":[{"value":"7 April 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 October 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1179"}}