{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T17:37:58Z","timestamp":1792949878963,"version":"4.5.0"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"7874","license":[{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2021,9,2]]},"DOI":"10.1038\/s41586-021-03817-4","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T06:03:18Z","timestamp":1626674598000},"page":"103-108","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":295,"title":["Broad sarbecovirus neutralization by a human monoclonal antibody"],"prefix":"10.1038","volume":"597","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2260-2577","authenticated-orcid":false,"given":"M. Alejandra","family":"Tortorici","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Czudnochowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6713-6904","authenticated-orcid":false,"given":"Tyler N.","family":"Starr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6025-6735","authenticated-orcid":false,"given":"Roberta","family":"Marzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9636-8330","authenticated-orcid":false,"given":"Alexandra C.","family":"Walls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizia","family":"Zatta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3590-9727","authenticated-orcid":false,"given":"John E.","family":"Bowen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7527-4434","authenticated-orcid":false,"given":"Stefano","family":"Jaconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Di Iulio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoqian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"De Marco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha K.","family":"Zepeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8198-0976","authenticated-orcid":false,"given":"Zhuoming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Beltramello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istvan","family":"Bartha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Housley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6103-8078","authenticated-orcid":false,"given":"Florian A.","family":"Lempp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8030-0219","authenticated-orcid":false,"given":"Laura E.","family":"Rosen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Exequiel","family":"Dellota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3991-7401","authenticated-orcid":false,"given":"Hannah","family":"Kaiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6200-9578","authenticated-orcid":false,"given":"Martin","family":"Montiel-Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4231-3422","authenticated-orcid":false,"given":"Jiayi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Addetia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Guarino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Culap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Sprugasci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Saliba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0216-6704","authenticated-orcid":false,"given":"Eneida","family":"Vetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Giacchetto-Sasselli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara Silacci","family":"Fregni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Abdelnabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6380-4917","authenticated-orcid":false,"given":"Shi-Yan Caroline","family":"Foo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2880-3927","authenticated-orcid":false,"given":"Colin","family":"Havenar-Daughton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1137-9322","authenticated-orcid":false,"given":"Michael A.","family":"Schmid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Benigni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Cameroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0033-7514","authenticated-orcid":false,"given":"Johan","family":"Neyts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6290-7677","authenticated-orcid":false,"given":"Amalio","family":"Telenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8580-7628","authenticated-orcid":false,"given":"Herbert W.","family":"Virgin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1564-8590","authenticated-orcid":false,"given":"Sean P. J.","family":"Whelan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1475-659X","authenticated-orcid":false,"given":"Gyorgy","family":"Snell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1267-3408","authenticated-orcid":false,"given":"Jesse D.","family":"Bloom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5797-1364","authenticated-orcid":false,"given":"Davide","family":"Corti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6019-8675","authenticated-orcid":false,"given":"David","family":"Veesler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5776-654X","authenticated-orcid":false,"given":"Matteo Samuele","family":"Pizzuto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,19]]},"reference":[{"key":"3817_CR1","doi-asserted-by":"publisher","first-page":"3426","DOI":"10.1016\/j.cell.2021.04.025","volume":"184","author":"X Deng","year":"2021","unstructured":"Deng, X. et al. Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant. Cell 184, 3426\u20133437 (2021).","journal-title":"Cell"},{"key":"3817_CR2","doi-asserted-by":"publisher","first-page":"n579","DOI":"10.1136\/bmj.n579","volume":"372","author":"R Challen","year":"2021","unstructured":"Challen, R. et al. Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012\/1: matched cohort study. Br. Med. J. 372, n579 (2021).","journal-title":"Br. Med. J."},{"key":"3817_CR3","doi-asserted-by":"publisher","first-page":"eabg3055","DOI":"10.1126\/science.abg3055","volume":"372","author":"NG Davies","year":"2021","unstructured":"Davies, N. G. et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science 372, eabg3055 (2021).","journal-title":"Science"},{"key":"3817_CR4","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/s41586-021-03402-9","volume":"592","author":"H Tegally","year":"2021","unstructured":"Tegally, H. et al. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature 592, 438\u2013443 (2021).","journal-title":"Nature"},{"key":"3817_CR5","doi-asserted-by":"publisher","unstructured":"McCallum, M. et al. SARS-CoV-2 immune evasion by the B.1.427\/B.1.429 variant of concern. Science\u00a0https:\/\/doi.org\/10.1126\/science.abi7994 (2021).","DOI":"10.1126\/science.abi7994"},{"key":"3817_CR6","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1038\/s41586-021-03324-6","volume":"592","author":"Z Wang","year":"2021","unstructured":"Wang, Z. et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature 592, 616\u2013622 (2021).","journal-title":"Nature"},{"key":"3817_CR7","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/s41586-021-03412-7","volume":"593","author":"DA Collier","year":"2021","unstructured":"Collier, D. A. et al. Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies. Nature 593, 136\u2013141 (2021).","journal-title":"Nature"},{"key":"3817_CR8","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1038\/s41591-021-01285-x","volume":"27","author":"CK Wibmer","year":"2021","unstructured":"Wibmer, C. K. et al. SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. Nat. Med. 27, 622\u2013625 (2021).","journal-title":"Nat. Med."},{"key":"3817_CR9","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1038\/s41591-021-01294-w","volume":"27","author":"RE Chen","year":"2021","unstructured":"Chen, R. E. et al. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nat. Med. 27, 717\u2013726 (2021).","journal-title":"Nat. Med."},{"key":"3817_CR10","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1056\/NEJMoa2102214","volume":"384","author":"SA Madhi","year":"2021","unstructured":"Madhi, S. A. et al. Efficacy of the ChAdOx1 nCoV-19 Covid-19 vaccine against the B.1.351 variant. N. Engl. J. Med. 384, 1885\u20131898 (2021).","journal-title":"N. Engl. J. Med."},{"key":"3817_CR11","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/bs.aivir.2019.08.002","volume":"105","author":"MA Tortorici","year":"2019","unstructured":"Tortorici, M. A. & Veesler, D. Structural insights into coronavirus entry. Adv. Virus Res. 105, 93\u2013116 (2019).","journal-title":"Adv. Virus Res."},{"key":"3817_CR12","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 (2020).","journal-title":"Cell"},{"key":"3817_CR13","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":"3817_CR14","doi-asserted-by":"publisher","first-page":"2738","DOI":"10.1007\/s00018-004-4242-5","volume":"61","author":"JH Kuhn","year":"2004","unstructured":"Kuhn, J. H., Li, W., Choe, H. & Farzan, M. Angiotensin-converting enzyme 2: a functional receptor for SARS coronavirus. Cell. Mol. Life Sci. 61, 2738\u20132743 (2004).","journal-title":"Cell. Mol. Life Sci."},{"key":"3817_CR15","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","volume":"181","author":"M Hoffmann","year":"2020","unstructured":"Hoffmann, M. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181, 271\u2013280 (2020).","journal-title":"Cell"},{"key":"3817_CR16","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":"3817_CR17","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 (2020).","journal-title":"Cell"},{"key":"3817_CR18","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1126\/science.abf6840","volume":"371","author":"AA Cohen","year":"2021","unstructured":"Cohen, A. A. et al. Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice. Science 371, 735\u2013741 (2021).","journal-title":"Science"},{"key":"3817_CR19","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":"3817_CR20","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1126\/science.abf4830","volume":"371","author":"CG Rappazzo","year":"2021","unstructured":"Rappazzo, C. G. et al. Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody. Science 371, 823\u2013829 (2021).","journal-title":"Science"},{"key":"3817_CR21","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1126\/science.abe3354","volume":"370","author":"MA Tortorici","year":"2020","unstructured":"Tortorici, M. A. et al. Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms. Science 370, 950\u2013957 (2020).","journal-title":"Science"},{"key":"3817_CR22","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/s41586-020-2349-y","volume":"583","author":"D Pinto","year":"2020","unstructured":"Pinto, D. et al. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature 583, 290\u2013295 (2020).","journal-title":"Nature"},{"key":"3817_CR23","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-021-03426-1","volume":"593","author":"NG Davies","year":"2021","unstructured":"Davies, N. G. et al. Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7. Nature 593, 270\u2013274 (2021).","journal-title":"Nature"},{"key":"3817_CR24","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1016\/j.cell.2021.01.037","volume":"184","author":"EC Thomson","year":"2021","unstructured":"Thomson, E. C. et al. Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity. Cell 184, 1171\u20131187 (2021).","journal-title":"Cell"},{"key":"3817_CR25","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1126\/science.abh2644","volume":"372","author":"NR Faria","year":"2021","unstructured":"Faria, N. R. et al. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. Science 372, 815\u2013821 (2021).","journal-title":"Science"},{"key":"3817_CR26","doi-asserted-by":"publisher","unstructured":"Starr, T. N. et al. SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape. Nature\u00a0https:\/\/doi.org\/10.1038\/s41586-021-03807-6 (2021).","DOI":"10.1038\/s41586-021-03807-6"},{"key":"3817_CR27","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/s41586-020-2852-1","volume":"588","author":"CO Barnes","year":"2020","unstructured":"Barnes, C. O. et al. SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature 588, 682\u2013687 (2020).","journal-title":"Nature"},{"key":"3817_CR28","doi-asserted-by":"publisher","unstructured":"Cathcart, A L. et al. The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2. Preprint at https:\/\/doi.org\/10.1101\/2021.03.09.434607 (2021).","DOI":"10.1101\/2021.03.09.434607"},{"key":"3817_CR29","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1016\/j.cell.2020.08.012","volume":"182","author":"TN Starr","year":"2020","unstructured":"Starr, T. N. et al. Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding. Cell 182, 1295\u20131310 (2020).","journal-title":"Cell"},{"key":"3817_CR30","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/j.chom.2020.07.018","volume":"28","author":"JB Case","year":"2020","unstructured":"Case, J. B. et al. Replication-competent vesicular stomatitis virus vaccine vector protects against SARS-CoV-2-mediated pathogenesis in mice. Cell Host Microbe 28, 465\u2013474 (2020).","journal-title":"Cell Host Microbe"},{"key":"3817_CR31","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.chom.2021.01.014","volume":"29","author":"Z Liu","year":"2021","unstructured":"Liu, Z. et al. Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization. Cell Host Microbe 29, 477\u2013488 (2021).","journal-title":"Cell Host Microbe"},{"key":"3817_CR32","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.e6 (2020).","journal-title":"Cell Host Microbe"},{"key":"3817_CR33","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1016\/j.cell.2018.12.028","volume":"176","author":"AC Walls","year":"2019","unstructured":"Walls, A. C. et al. Unexpected receptor functional mimicry elucidates activation of coronavirus fusion. Cell 176, 1026\u20131039 (2019).","journal-title":"Cell"},{"key":"3817_CR34","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1126\/science.abc7424","volume":"369","author":"AZ Wec","year":"2020","unstructured":"Wec, A. Z. et al. Broad neutralization of SARS-related viruses by human monoclonal antibodies. Science 369, 731\u2013736 (2020).","journal-title":"Science"},{"key":"3817_CR35","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":"3817_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19684-y","volume":"11","author":"R Boudewijns","year":"2020","unstructured":"Boudewijns, R. et al. STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters. Nat. Commun. 11, 5838 (2020).","journal-title":"Nat. Commun."},{"key":"3817_CR37","doi-asserted-by":"publisher","first-page":"e20201993","DOI":"10.1084\/jem.20201993","volume":"218","author":"A Sch\u00e4fer","year":"2021","unstructured":"Sch\u00e4fer, A. et al. Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo. J. Exp. Med. 218, e20201993 (2021).","journal-title":"J. Exp. Med."},{"key":"3817_CR38","doi-asserted-by":"publisher","first-page":"1804","DOI":"10.1016\/j.cell.2021.02.026","volume":"184","author":"ES Winkler","year":"2021","unstructured":"Winkler, E. S. et al. Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions and monocytes for optimal therapeutic protection. Cell 184,1804\u20131820 (2021).","journal-title":"Cell"},{"key":"3817_CR39","doi-asserted-by":"publisher","first-page":"103403","DOI":"10.1016\/j.ebiom.2021.103403","volume":"68","author":"R Abdelnabi","year":"2021","unstructured":"Abdelnabi, R. et al. Comparing infectivity and virulence of emerging SARS-CoV-2 variants in Syrian hamsters. EBioMedicine 68, 103403 (2021).","journal-title":"EBioMedicine"},{"key":"3817_CR40","doi-asserted-by":"publisher","unstructured":"Walls, A. C. et al. Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines. Preprint at https:\/\/doi.org\/10.1101\/2021.03.15.435528 (2021).","DOI":"10.1101\/2021.03.15.435528"},{"key":"3817_CR41","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1038\/nm.3985","volume":"21","author":"VD Menachery","year":"2015","unstructured":"Menachery, V. D. et al. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nat. Med. 21, 1508\u20131513 (2015).","journal-title":"Nat. Med."},{"key":"3817_CR42","doi-asserted-by":"publisher","first-page":"3048","DOI":"10.1073\/pnas.1517719113","volume":"113","author":"VD Menachery","year":"2016","unstructured":"Menachery, V. D. et al. SARS-like WIV1-CoV poised for human emergence. Proc. Natl Acad. Sci. USA 113, 3048\u20133053 (2016).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3817_CR43","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/nature12711","volume":"503","author":"XY Ge","year":"2013","unstructured":"Ge, X. Y. et al. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature 503, 535\u2013538 (2013).","journal-title":"Nature"},{"key":"3817_CR44","doi-asserted-by":"publisher","unstructured":"Martinez, D. R. et al. Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice. Science\u00a0https:\/\/doi.org\/10.1126\/science.abi4506 (2021).","DOI":"10.1126\/science.abi4506"},{"key":"3817_CR45","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s12862-020-01732-2","volume":"21","author":"V Makarenkov","year":"2021","unstructured":"Makarenkov, V., Mazoure, B., Rabusseau, G. & Legendre, P. Horizontal gene transfer and recombination analysis of SARS-CoV-2 genes helps discover its close relatives and shed light on its origin. BMC Ecol. Evol. 21, 5 (2021).","journal-title":"BMC Ecol. Evol."},{"key":"3817_CR46","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.chom.2021.02.003","volume":"29","author":"AJ Greaney","year":"2021","unstructured":"Greaney, A. J. et al. Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies. Cell Host Microbe 29, 463\u2013476 (2021).","journal-title":"Cell Host Microbe"},{"key":"3817_CR47","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1016\/j.cell.2020.10.043","volume":"183","author":"AC Walls","year":"2020","unstructured":"Walls, A. C. et al. Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2. Cell 183, 1367\u20131382 (2020).","journal-title":"Cell"},{"key":"3817_CR48","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.chom.2019.09.016","volume":"26","author":"D Pinto","year":"2019","unstructured":"Pinto, D. et al. Structural basis for broad HIV-1 neutralization by the MPER-specific human broadly neutralizing antibody LN01. Cell Host Microbe 26, 623\u2013637 (2019).","journal-title":"Cell Host Microbe"},{"key":"3817_CR49","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-6-31","volume":"6","author":"GSC Slater","year":"2005","unstructured":"Slater, G. S. C & Birney, E. Automated generation of heuristics for biological sequence comparison. BMC Bioinformatics 6, 31 (2005).","journal-title":"BMC Bioinformatics"},{"key":"3817_CR50","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1093\/molbev\/mst010","volume":"30","author":"K Katoh","year":"2013","unstructured":"Katoh, K. & Standley, D. M. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol. Biol. Evol. 30, 772\u2013780 (2013).","journal-title":"Mol. Biol. Evol."},{"key":"3817_CR51","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15562-9","volume":"11","author":"X Ou","year":"2020","unstructured":"Ou, X. et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat. Commun. 11, 1620 (2020).","journal-title":"Nat. Commun."},{"key":"3817_CR52","doi-asserted-by":"publisher","first-page":"513","DOI":"10.3390\/v12050513","volume":"12","author":"KHD Crawford","year":"2020","unstructured":"Crawford, K. H. D. et al. Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays. Viruses 12, 513 (2020).","journal-title":"Viruses"},{"key":"3817_CR53","doi-asserted-by":"publisher","first-page":"14764","DOI":"10.1073\/pnas.94.26.14764","volume":"94","author":"A Takada","year":"1997","unstructured":"Takada, A. et al. A system for functional analysis of Ebola virus glycoprotein. Proc. Natl Acad. Sci. USA 94, 14764\u201314769 (1997).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3817_CR54","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19055-7","volume":"11","author":"X Xie","year":"2020","unstructured":"Xie, X. et al. A nanoluciferase SARS-CoV-2 for rapid neutralization testing and screening of anti-infective drugs for COVID-19. Nat. Commun. 11, 5214 (2020).","journal-title":"Nat. Commun."},{"key":"3817_CR55","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","volume":"27","author":"LJ Reed","year":"1938","unstructured":"Reed, L. J. & Muench, H. A simple method of estimating fifty per cent endpoints. Am. J. Epidemiol. 27, 493\u2013497 (1938).","journal-title":"Am. J. Epidemiol."},{"key":"3817_CR56","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.chom.2020.11.007","volume":"29","author":"AJ Greaney","year":"2021","unstructured":"Greaney, A. J. et al. Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition. Cell Host Microbe 29, 44\u201357 (2021).","journal-title":"Cell Host Microbe"},{"key":"3817_CR57","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1126\/science.abf9302","volume":"371","author":"TN Starr","year":"2021","unstructured":"Starr, T. N. et al. Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. Science 371, 850\u2013854 (2021).","journal-title":"Science"},{"key":"3817_CR58","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1107\/S0907444909047337","volume":"66","author":"W Kabsch","year":"2010","unstructured":"Kabsch, W. Xds. Acta Crystallogr. D 66, 125\u2013132 (2010).","journal-title":"Acta Crystallogr. D"},{"key":"3817_CR59","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1107\/S0021889807021206","volume":"40","author":"AJ McCoy","year":"2007","unstructured":"McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658\u2013674 (2007).","journal-title":"J. Appl. Crystallogr."},{"key":"3817_CR60","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1107\/S0907444910007493","volume":"66","author":"P Emsley","year":"2010","unstructured":"Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486\u2013501 (2010).","journal-title":"Acta Crystallogr. D"},{"key":"3817_CR61","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1107\/S2059798318002425","volume":"74","author":"TI Croll","year":"2018","unstructured":"Croll, T. I. ISOLDE: a physically realistic environment for model building into low-resolution electron-density maps. Acta Crystallogr. D 74, 519\u2013530 (2018).","journal-title":"Acta Crystallogr. D"},{"key":"3817_CR62","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1107\/S0907444911001314","volume":"67","author":"GN Murshudov","year":"2011","unstructured":"Murshudov, G. N. et al. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr. D 67, 355\u2013367 (2011).","journal-title":"Acta Crystallogr. D"},{"key":"3817_CR63","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.jsb.2005.03.010","volume":"151","author":"C Suloway","year":"2005","unstructured":"Suloway, C. et al. Automated molecular microscopy: the new Leginon system. J. Struct. Biol. 151, 41\u201360 (2005).","journal-title":"J. Struct. Biol."},{"key":"3817_CR64","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1038\/s41592-019-0580-y","volume":"16","author":"D Tegunov","year":"2019","unstructured":"Tegunov, D. & Cramer, P. Real-time cryo-electron microscopy data preprocessing with Warp. Nat. Methods 16, 1146\u20131152 (2019).","journal-title":"Nat. Methods"},{"key":"3817_CR65","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":"3817_CR66","doi-asserted-by":"publisher","first-page":"e42166","DOI":"10.7554\/eLife.42166","volume":"7","author":"J Zivanov","year":"2018","unstructured":"Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018).","journal-title":"eLife"},{"key":"3817_CR67","doi-asserted-by":"publisher","first-page":"e18722","DOI":"10.7554\/eLife.18722","volume":"5","author":"D Kimanius","year":"2016","unstructured":"Kimanius, D., Forsberg, B. O., Scheres, S. H. & Lindahl, E. Accelerated cryo-EM structure determination with parallelisation using GPUs in RELION-2. eLife 5, e18722 (2016).","journal-title":"eLife"},{"key":"3817_CR68","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1038\/s41592-020-00990-8","volume":"17","author":"A Punjani","year":"2020","unstructured":"Punjani, A., Zhang, H. & Fleet, D. J. Non-uniform refinement: adaptive regularization improves single-particle cryo-EM reconstruction. Nat. Methods 17, 1214\u20131221 (2020).","journal-title":"Nat. Methods"},{"key":"3817_CR69","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1107\/S205225251801463X","volume":"6","author":"J Zivanov","year":"2019","unstructured":"Zivanov, J., Nakane, T. & Scheres, S. H. W. A Bayesian approach to beam-induced motion correction in cryo-EM single-particle analysis. IUCrJ 6, 5\u201317 (2019).","journal-title":"IUCrJ"},{"key":"3817_CR70","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ultramic.2013.06.004","volume":"135","author":"S Chen","year":"2013","unstructured":"Chen, S. et al. High-resolution noise substitution to measure overfitting and validate resolution in 3D structure determination by single particle electron cryomicroscopy. Ultramicroscopy 135, 24\u201335 (2013).","journal-title":"Ultramicroscopy"},{"key":"3817_CR71","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":"3817_CR72","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.str.2018.09.006","volume":"27","author":"B Frenz","year":"2019","unstructured":"Frenz, B. et al. Automatically fixing errors in glycoprotein structures with Rosetta. Structure 27, 134\u2013139 (2019).","journal-title":"Structure"},{"key":"3817_CR73","doi-asserted-by":"publisher","first-page":"e17219","DOI":"10.7554\/eLife.17219","volume":"5","author":"RY Wang","year":"2016","unstructured":"Wang, R. Y. et al. Automated structure refinement of macromolecular assemblies from cryo-EM maps using Rosetta. eLife 5, e17219 (2016).","journal-title":"eLife"},{"key":"3817_CR74","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1107\/S2059798319011471","volume":"75","author":"D Liebschner","year":"2019","unstructured":"Liebschner, D. et al. Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix. Acta Crystallogr. D 75, 861\u2013877 (2019).","journal-title":"Acta Crystallogr. D"},{"key":"3817_CR75","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 66, 12\u201321 (2010).","journal-title":"Acta Crystallogr. D"},{"key":"3817_CR76","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1038\/nsmb.3115","volume":"22","author":"J Agirre","year":"2015","unstructured":"Agirre, J. et al. Privateer: software for the conformational validation of carbohydrate structures. Nat. Struct. Mol. Biol. 22, 833\u2013834 (2015).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"3817_CR77","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1002\/pro.3235","volume":"27","author":"TD Goddard","year":"2018","unstructured":"Goddard, T. D. et al. UCSF ChimeraX: meeting modern challenges in visualization and analysis. Protein Sci. 27, 14\u201325 (2018).","journal-title":"Protein Sci."},{"key":"3817_CR78","doi-asserted-by":"publisher","unstructured":"Pinto, D. et al. A human antibody that broadly neutralizes betacoronaviruses protects against SARS-CoV-2 by blocking the fusion machinery. Preprint at https:\/\/doi.org\/10.1101\/2021.05.09.442808 (2021).","DOI":"10.1101\/2021.05.09.442808"}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41586-021-03817-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-021-03817-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-021-03817-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T08:05:00Z","timestamp":1630483500000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-021-03817-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,19]]},"references-count":78,"journal-issue":{"issue":"7874","published-print":{"date-parts":[[2021,9,2]]}},"alternative-id":["3817"],"URL":"https:\/\/doi.org\/10.1038\/s41586-021-03817-4","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,19]]},"assertion":[{"value":"29 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"N.C., R.M., F.Z., S.J., J.D.I., A.D.M., D.P., M.B., I.B., M.H., F.A.L., L.E.R, E.D. Jr, H. K., M.M.-R., J.Z., K.C., N.S., C.S., E.V., I.G.-S., C.S.F., C.H.-D., M.A.S., F.B., E.C., A.T., G.S., H.W.V., D.C. and M.S.P. are employees of Vir Biotechnology Inc. and may hold shares in Vir Biotechnology Inc. D.C. is currently listed as an inventor on multiple patent applications, which disclose the subject matter described in this Article. The laboratory of J.N. has received sponsored research agreements from Vir Biotechnology Inc. After the submission of the initial version of this study, J.D.B. began consulting for Moderna on viral evolution and epidemiology. J.D.B. has the potential to receive a share of IP revenue as an inventor on a Fred Hutchinson Cancer Research Center-optioned technology and patent (application WO2020006494) related to deep-mutational scanning of viral proteins. H.W.V. is a founder of PierianDx and Casma Therapeutics. Neither company provided funding for this work or is performing related work. D.V. is a consultant for Vir Biotechnology Inc. The laboratory of D.V. has received a sponsored research agreement from Vir Biotechnology Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}