{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:34:47Z","timestamp":1787009687126,"version":"build-2736575974"},"reference-count":99,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":160,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic, has produced unprecedented numbers of structures of the Spike protein. In this study, we present a comprehensive analysis of 1560 published structures, covering most major variants that emerged throughout the pandemic, diverse heteromerization, and interacting complexes. Using interaction-energy-informed geometric clustering, we identify 14 structurally distinct epitopes based on their conformational specificity, shared interface with angiotensin-converting enzyme 2 (ACE2), and glycosylation patterns. Our per-residue interaction evaluations accurately predict antibody recognition sites and correlate strongly with deep mutational scanning data, enabling immune escape predictions for future variants. To complement this structural analysis, we integrate longitudinal genomic data from nearly 3 million viral sequences, linking mutational patterns to changes in Spike\u2019s conformational dynamics. Our findings reveal two distinct evolutionary trade-offs driving immune escape. First, we confirm an enthalpic trade-off, where mutations in the receptor-binding motif (RBM) enhance immune escape at the cost of weakened ACE2 binding. Second, we introduce an entropic trade-off, showing that mutations outside the RBM modulate Spike\u2019s conformational equilibrium, reducing open-state occupancy to evade immune detection\u2014without directly altering the ACE2-binding interface. With these analyses, this work not only highlights the different functional effects of mutations across SARS-CoV-2 Spike variants but also reveals the complex interplay of evolutionary forces shaping the evolution of the SARS-CoV-2 Spike protein over the course of the pandemic.<\/jats:p>","DOI":"10.1093\/ve\/veaf027","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T07:55:38Z","timestamp":1749196538000},"source":"Crossref","is-referenced-by-count":6,"title":["Comprehensive analysis of SARS-CoV-2 Spike evolution: epitope classification and immune escape prediction"],"prefix":"10.1093","volume":"11","author":[{"given":"Nat\u00e1lia Fagundes Borges","family":"Teruel","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al , Montreal,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5091-6282","authenticated-orcid":false,"given":"Matthew","family":"Crown","sequence":"additional","affiliation":[{"name":"Hub for Biotechnology in the Built Environment, Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University , Newcastle upon Tyne NE1 8ST,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Rajsbaum","sequence":"additional","affiliation":[{"name":"Center for Virus-Host-Innate-Immunity, RBHS Institute for Infectious and Inflammatory Diseases, and Department of Medicine, New Jersey Medical School, Rutgers University , 205 S. Orange Avenue, Newark, NJ 07103,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6847-1525","authenticated-orcid":false,"given":"Matthew","family":"Bashton","sequence":"additional","affiliation":[{"name":"Hub for Biotechnology in the Built Environment, Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University , Newcastle upon Tyne NE1 8ST,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6971-7224","authenticated-orcid":false,"given":"Rafael","family":"Najmanovich","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al , Montreal,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"2025071112133266800_R1","first-page":"2020","article-title":"A glycan cluster on the SARS-CoV-2 spike ectodomain is recognized by Fab-dimerized glycan- reactive antibodies","author":"Acharya","year":"2020"},{"key":"2025071112133266800_R2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2020.166762","article-title":"Subtle influence of ACE2 glycan processing on SARS-CoV-2 recognition","volume":"433","author":"Allen","year":"2021","journal-title":"J Mol Biol"},{"key":"2025071112133266800_R3","article-title":"Evolving spike- protein N-glycosylation in SARS-CoV-2 variants","author":"Baboo","year":"2023"},{"key":"2025071112133266800_R4","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/s41586-020-2852-1","article-title":"SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies","volume":"588","author":"Barnes","year":"2020","journal-title":"Nature"},{"key":"2025071112133266800_R5","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1016\/j.cell.2020.06.025","article-title":"Structures of human antibodies bound to SARS-CoV-2 spike reveal common epitopes and recurrent features of antibodies","volume":"182","author":"Barnes","year":"2020","journal-title":"Cell"},{"key":"2025071112133266800_R6","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.70658","article-title":"Effects of common mutations in the SARS-CoV-2 spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics","volume":"10","author":"Barton","year":"2021","journal-title":"eLife"},{"key":"2025071112133266800_R7","doi-asserted-by":"publisher","first-page":"D41","DOI":"10.1093\/nar\/gkx1094","article-title":"GenBank","volume":"46","author":"Benson","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2025071112133266800_R8","doi-asserted-by":"publisher","DOI":"10.3390\/v14020295","article-title":"Computational analysis of mutations in the receptor-binding domain of SARS-CoV-2 spike and their effects on antibody binding","volume":"14","author":"Bozdaganyan","year":"2022","journal-title":"Viruses"},{"key":"2025071112133266800_R9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36745-0","article-title":"Structural dynamics in the evolution of SARS-CoV-2 spike glycoprotein","volume":"14","author":"Calvaresi","year":"2023","journal-title":"Nat Commun"},{"key":"2025071112133266800_R10","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1038\/s41586-021-04386-2","article-title":"Broadly neutralizing antibodies overcome SARS-CoV-2 omicron antigenic shift","volume":"602","author":"Cameroni","year":"2022","journal-title":"Nature"},{"key":"2025071112133266800_R11","first-page":"521","article-title":"Imprinted SARS-CoV-2 humoral immunity induces convergent omicron RBD evolution","volume":"614","author":"Cao","year":"2023","journal-title":"Nature"},{"key":"2025071112133266800_R12","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/s41586-022-04980-y","article-title":"BA. 2.12. 1, BA. 4 and BA. 5 escape antibodies elicited by omicron infection","volume":"608","author":"Cao","year":"2022","journal-title":"Nature"},{"key":"2025071112133266800_R13","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1097\/JS9.0000000000000219","article-title":"Recently emerged omicron subvariant BF. 7 and its R346T mutation in the RBD region reveal increased transmissibility and higher resistance to neutralization antibodies: need to understand more under the current scenario of rising cases in China and fears of driving a new wave of the COVID-19 pandemic","volume":"109","author":"Chakraborty","year":"2023","journal-title":"Int J Surg"},{"key":"2025071112133266800_R14","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1097\/JS9.0000000000000246","article-title":"The SARS-CoV-2 Omicron recombinant subvariants XBB, XBB. 1, and XBB. 1.5 are expanding rapidly with unique mutations, antibody evasion, and immune escape properties\u2013an alarming global threat of a surge in COVID-19 cases again?","volume":"109","author":"Chakraborty","year":"2023","journal-title":"Int J Surg"},{"key":"2025071112133266800_R15","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1093\/bioinformatics\/btab856","article-title":"CoV-spectrum: analysis of globally shared SARS-CoV-2 data to identify and characterize new variants","volume":"38","author":"Chen","year":"2022","journal-title":"Bioinformatics"},{"key":"2025071112133266800_R16","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/s41577-022-00784-3","article-title":"Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses","volume":"23","author":"Chen","year":"2023","journal-title":"Nat Rev Immunol"},{"key":"2025071112133266800_R17","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/s41586-021-03412-7","article-title":"Sensitivity of SARS-CoV-2 B. 1.1. 7 to mRNA vaccine-elicited antibodies","volume":"593","author":"Collier","year":"2021","journal-title":"Nature"},{"key":"2025071112133266800_R18","doi-asserted-by":"publisher","first-page":"3827","DOI":"10.1093\/bioinformatics\/btac391","article-title":"Spear: systematic protein annotator","volume":"38","author":"Crown","year":"2022","journal-title":"Bioinformatics"},{"key":"2025071112133266800_R19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.691715","article-title":"Epitope classification and RBD binding properties of neutralizing antibodies against SARS-CoV-2 variants of concern","volume":"12","author":"Deshpande","year":"2021","journal-title":"Front Immunol"},{"key":"2025071112133266800_R20","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1002\/gch2.1018","article-title":"Data, disease and diplomacy: GISAID\u2019s innovative contribution to global health","volume":"1","author":"Elbe","year":"2017","journal-title":"Glob Chall"},{"key":"2025071112133266800_R21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41392-022-00997-x","article-title":"SARS-CoV-2 omicron variant: recent progress and future perspectives","volume":"7","author":"Fan","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"2025071112133266800_R22","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2021.109627","article-title":"One-shot identification of SARS-CoV-2 S RBD escape mutants using yeast screening","volume":"36","author":"Francino-Urdaniz","year":"2021","journal-title":"Cell Rep"},{"key":"2025071112133266800_R23","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1107\/S2059798322011901","article-title":"Errors in structural biology are not the exception","volume":"79","author":"Gao","year":"2023","journal-title":"Acta Crystallogr Sect D: Struct Biol"},{"key":"2025071112133266800_R24","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73490","article-title":"Comprehensive characterization of the antibody responses to SARS-CoV-2 spike protein finds additional vaccine-induced epitopes beyond those for mild infection","volume":"11","author":"Garrett","year":"2022","journal-title":"eLife"},{"key":"2025071112133266800_R25","doi-asserted-by":"publisher","first-page":"e00249","DOI":"10.1128\/jvi.00249-22","article-title":"Structural basis for human receptor recognition by SARS-CoV-2 omicron variant BA. 1","volume":"96","author":"Geng","year":"2022","journal-title":"J Virol"},{"key":"2025071112133266800_R26","doi-asserted-by":"publisher","first-page":"2050","DOI":"10.1016\/j.molcel.2022.03.028","article-title":"Structural diversity of the SARS-CoV-2 Omicron spike","volume":"82","author":"Gobeil","year":"2022","journal-title":"Mol Cell"},{"key":"2025071112133266800_R27","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.108630","article-title":"D614G mutation alters SARS-CoV-2 spike conformation and enhances protease cleavage at the S1\/S2 junction","volume":"34","author":"Gobeil","year":"2021","journal-title":"Cell Rep"},{"key":"2025071112133266800_R28","doi-asserted-by":"publisher","DOI":"10.1126\/science.abi6226","article-title":"Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity","volume":"373","author":"Gobeil","year":"2021","journal-title":"Science"},{"key":"2025071112133266800_R29","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1080\/07388551.2017.1416577","article-title":"Impact of host cell line choice on glycan profile","volume":"38","author":"Goh","year":"2018","journal-title":"Crit Rev Biotechnol"},{"key":"2025071112133266800_R30","article-title":"The glycosylation in SARS-CoV-2 and its receptor ACE2","volume":"6","author":"Gong","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"2025071112133266800_R31","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-71748-7","article-title":"Analysis of the SARS-CoV-2 spike protein glycan shield reveals implications for immune recognition","volume":"10","author":"Grant","year":"2020","journal-title":"Sci Rep"},{"key":"2025071112133266800_R32","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/veac021","article-title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","volume":"8","author":"Greaney","year":"2022","journal-title":"Virus Evolut"},{"key":"2025071112133266800_R33","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2022.100564","article-title":"Rapid emergence of omicron sublineages expressing spike protein R346T","volume":"24","author":"Groenheit","year":"2023","journal-title":"Lancet Reg Health Eur"},{"key":"2025071112133266800_R34","doi-asserted-by":"publisher","first-page":"4121","DOI":"10.1093\/bioinformatics\/bty407","article-title":"Nextstrain: real-time tracking of pathogen evolution","volume":"34","author":"Hadfield","year":"2018","journal-title":"Bioinformatics"},{"key":"2025071112133266800_R35","doi-asserted-by":"publisher","first-page":"4405","DOI":"10.1021\/acs.jcim.3c00134","article-title":"Solvent accessibility promotes rotamer errors during protein modeling with major side-chain prediction programs","volume":"63","author":"Hameduh","year":"2023","journal-title":"J Chem Inf Model"},{"key":"2025071112133266800_R36","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.cell.2022.01.001","article-title":"Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2","volume":"185","author":"Han","year":"2022","journal-title":"Cell"},{"key":"2025071112133266800_R37","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1039\/D1SC04832E","article-title":"Fine-tuning the spike: role of the nature and topology of the glycan shield in the structure and dynamics of the SARS-CoV-2 S","volume":"13","author":"Harbison","year":"2022","journal-title":"Chem Sci"},{"key":"2025071112133266800_R38","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/s41579-021-00573-0","article-title":"SARS-CoV-2 variants, spike mutations and immune escape","volume":"19","author":"Harvey","year":"2021","journal-title":"Nat Rev Microbiol"},{"key":"2025071112133266800_R39","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1126\/science.abh2315","article-title":"Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study","volume":"374","author":"Hastie","year":"2021","journal-title":"Science"},{"key":"2025071112133266800_R40","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1038\/s41586-022-04581-9","article-title":"Molecular basis of receptor binding and antibody neutralization of omicron","volume":"604","author":"Hong","year":"2022","journal-title":"Nature"},{"key":"2025071112133266800_R41","doi-asserted-by":"publisher","first-page":"4425","DOI":"10.1021\/acs.jcim.1c00560","article-title":"Key interacting residues between RBD of SARS-CoV-2 and ACE2 receptor: combination of molecular dynamics simulation and density functional calculation","volume":"61","author":"Jawad","year":"2021","journal-title":"J Chem Inf Model"},{"key":"2025071112133266800_R42","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/jcc.27025","article-title":"Binding of human ACE2 and RBD of Omicron enhanced by unique interaction patterns among SARS-CoV-2 variants of concern","volume":"44","author":"Kim","year":"2023","journal-title":"J Comput Chem"},{"key":"2025071112133266800_R43","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105720","article-title":"The SARS-CoV-2 spike S375F mutation characterizes the omicron BA. 1 variant","volume":"25","author":"Kimura","year":"2022","journal-title":"Iscience"},{"key":"2025071112133266800_R44","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2021.167058","article-title":"Experimental evidence for enhanced receptor binding by rapidly spreading SARS-CoV-2 variants","volume":"433","author":"Laffeber","year":"2021","journal-title":"J Mol Biol"},{"key":"2025071112133266800_R45","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1016\/j.cell.2020.07.012","article-title":"The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity","volume":"182","author":"Li","year":"2020","journal-title":"Cell"},{"key":"2025071112133266800_R46","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/nature02145","article-title":"Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus","volume":"426","author":"Li","year":"2003","journal-title":"Nature"},{"key":"2025071112133266800_R47","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1038\/s44318-024-00062-z","article-title":"Key mechanistic features of the trade-off between antibody escape and host cell binding in the SARS-CoV-2 omicron variant spike proteins","volume":"43","author":"Li","year":"2024","journal-title":"EMBO J"},{"key":"2025071112133266800_R48","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-023-00607-2","article-title":"Cryo-em structures of SARS-CoV-2 BA. 2-derived subvariants spike in complex with ACE2 receptor","volume":"9","author":"Li","year":"2023","journal-title":"Cell Discov"},{"key":"2025071112133266800_R49","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwae206","article-title":"Spike N354 glycosylation augments SARS-CoV-2 fitness for human adaptation through structural plasticity","volume":"11","author":"Liu","year":"2024","journal-title":"Natl Sci Rev"},{"key":"2025071112133266800_R50","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/S0140-6736(20)30251-8","article-title":"Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding","volume":"395","author":"Lu","year":"2020","journal-title":"Lancet"},{"key":"2025071112133266800_R51","doi-asserted-by":"publisher","first-page":"3369","DOI":"10.1093\/bioinformatics\/btab189","article-title":"The NRGTEN python package: an extensible toolkit for coarse-grained normal mode analysis of proteins, nucleic acids, small molecules and their complexes","volume":"37","author":"Mailhot","year":"2021","journal-title":"Bioinformatics"},{"key":"2025071112133266800_R52","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1126\/science.abn7760","article-title":"SARS-CoV-2 omicron variant: antibody evasion and cryo-EM structure of spike protein\u2013ACE2 complex","volume":"375","author":"Mannar","year":"2022","journal-title":"Science"},{"key":"2025071112133266800_R53","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2020.11.1904","article-title":"The SARS-CoV-2 spike variant D614G favors an open conformational state","volume":"120","author":"Mansbach","year":"2021","journal-title":"Biophys J"},{"key":"2025071112133266800_R54","article-title":"COVID-19 Genomics UK (COG-UK) consortium","volume":"9","author":"Marjanovic","year":"2022","journal-title":"Rand Health Q"},{"key":"2025071112133266800_R55","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1126\/science.abn8652","article-title":"Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement","volume":"375","author":"McCallum","year":"2022","journal-title":"Science"},{"key":"2025071112133266800_R56","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/s41586-021-03944-y","article-title":"SARS-COV-2 B. 1.617. 2 Delta variant replication and immune evasion","volume":"599","author":"Mlcochova","year":"2021","journal-title":"Nature"},{"key":"2025071112133266800_R57","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34506-z","article-title":"Compensatory epistasis maintains ACE2 affinity in SARS-CoV-2 Omicron BA. 1","volume":"13","author":"Moulana","year":"2022","journal-title":"Nat Commun"},{"key":"2025071112133266800_R58","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2023.107394","article-title":"Selection for immune evasion in SARS-CoV-2 revealed by high-resolution epitope mapping and sequence analysis","volume":"26","author":"N\u2019Guessan","year":"2023","journal-title":"Iscience"},{"key":"2025071112133266800_R59","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2020.11.359","article-title":"Exploring the role of glycans in the interaction of SARS-CoV-2 RBD and human receptor ACE2","volume":"120","author":"Nguyen","year":"2021","journal-title":"Biophys J"},{"key":"2025071112133266800_R60","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15562-9","article-title":"Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-COV","volume":"11","author":"Ou","year":"2020","journal-title":"Nat Commun"},{"key":"2025071112133266800_R61","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adp9279","article-title":"SARS-CoV-2 JN. 1 variant evasion OF IGHV3-53\/3-66 B cell germlines","volume":"9","author":"Paciello","year":"2024","journal-title":"Sci Immunol"},{"key":"2025071112133266800_R62","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-04138-6","article-title":"SARS-CoV-2 spike opening dynamics and energetics reveal the individual roles of glycans and their collective impact","volume":"5","author":"Pang","year":"2022","journal-title":"Commun Biol"},{"key":"2025071112133266800_R63","article-title":"Characteristics of JN. 1-derived SARS-CoV-2 subvariants slip, flirt, and kp. 2 in neutralization escape, infectivity and membrane fusion","author":"Pei","year":"2024"},{"key":"2025071112133266800_R64","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1016\/j.cell.2020.09.037","article-title":"Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology","volume":"183","author":"Piccoli","year":"2020","journal-title":"Cell"},{"key":"2025071112133266800_R65","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/s41586-021-04389-z","article-title":"Considerable escape of SARS-CoV-2 omicron to antibody neutralization","volume":"602","author":"Planas","year":"2022","journal-title":"Nature"},{"key":"2025071112133266800_R66","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.chom.2022.11.012","article-title":"Enhanced neutralization resistance of SARS-CoV-2 omicron subvariants BQ. 1, BQ. 1.1, BA. 4.6, BF. 7, and BA. 2.75. 2","volume":"31","author":"Qu","year":"2023","journal-title":"Cell Host Microbe"},{"key":"2025071112133266800_R67","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1010822","article-title":"Antibody accessibility determines location of spike surface mutations in SARS-CoV-2 variants","volume":"19","author":"Ren von Bu\u00a8low","year":"2023","journal-title":"PLOS Comput Biol"},{"key":"2025071112133266800_R68","doi-asserted-by":"publisher","first-page":"2742","DOI":"10.1093\/bioinformatics\/btac202","article-title":"Impact of protein conformational diversity on alphafold predictions","volume":"38","author":"Saldan\u02dco","year":"2022","journal-title":"Bioinformatics"},{"key":"2025071112133266800_R69","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","article-title":"Comparative protein modelling by satisfaction of spatial restraints","volume":"234","author":"\u0160ali","year":"1993","journal-title":"J Mol Biol"},{"key":"2025071112133266800_R70","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.str.2023.11.015","article-title":"Antibody targeting of conserved sites of vulnerability on the SARS-CoV-2 spike receptor-binding domain","volume":"32","author":"Sankhala","year":"2024","journal-title":"Structure"},{"key":"2025071112133266800_R71","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-022-02312-5","article-title":"Human serum from SARS-CoV-2-vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 omicron variant","volume":"20","author":"Schubert","year":"2022","journal-title":"BMC Med"},{"key":"2025071112133266800_R72","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2023.168187","article-title":"Free energy perturbation calculations of mutation effects on SARS-CoV-2 RBD:: ACE2 binding affinity","volume":"435","author":"Sergeeva","year":"2023","journal-title":"J Mol Biol"},{"key":"2025071112133266800_R73","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-33088-0","article-title":"Site specific N-and O-glycosylation mapping of the spike proteins of SARS-CoV-2 variants of concern","volume":"13","author":"Shajahan","year":"2023","journal-title":"Sci Rep"},{"key":"2025071112133266800_R74","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd4250","article-title":"Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity","volume":"370","author":"Shrock","year":"2020","journal-title":"Science"},{"key":"2025071112133266800_R75","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2017.22.13.30494","article-title":"GISAID: global initiative on sharing all influenza data \u2013 from vision to reality","volume":"22","author":"Shu","year":"2017","journal-title":"Eurosurveillance"},{"key":"2025071112133266800_R76","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1002\/pro.2829","article-title":"Ab-bind: antibody binding mutational database for computational affinity predictions","volume":"25","author":"Sirin","year":"2016","journal-title":"Protein Sci"},{"key":"2025071112133266800_R77","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1016\/j.cell.2020.08.012","article-title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","volume":"182","author":"Starr","year":"2020","journal-title":"cell"},{"key":"2025071112133266800_R78","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1038\/s41557-021-00758-3","article-title":"A glycan gate controls opening of the SARS-CoV-2 spike protein","volume":"13","author":"Sztain","year":"2021","journal-title":"Nat Chem"},{"key":"2025071112133266800_R79","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btad608","article-title":"Surfaces: a software to quantify and visualize interactions within and between proteins and ligands","volume":"39","author":"Teruel","year":"2023","journal-title":"Bioinformatics"},{"key":"2025071112133266800_R80","first-page":"2021","article-title":"Computational analysis of the effect of SARS-CoV-2 variant omicron spike protein mutations on dynamics, ACE2 binding and propensity for immune escape","author":"Teruel","year":"2021"},{"key":"2025071112133266800_R81","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009286","article-title":"Modelling conformational state dynamics and its role on infection for SARS-CoV-2 spike protein variants","volume":"17","author":"Teruel","year":"2021","journal-title":"PLOS Computat Biol"},{"key":"2025071112133266800_R82","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.69091","article-title":"N501y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2","volume":"10","author":"Tian","year":"2021","journal-title":"eLife"},{"key":"2025071112133266800_R83","doi-asserted-by":"publisher","first-page":"4587","DOI":"10.1021\/acs.jproteome.0c00654","article-title":"Molecular simulations and network modeling reveal an allosteric signaling in the SARS-CoV-2 spike proteins","volume":"19","author":"Verkhivker","year":"2020","journal-title":"J Proteome Res"},{"key":"2025071112133266800_R84","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","article-title":"Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein","volume":"181","author":"Walls","year":"2020","journal-title":"Cell"},{"key":"2025071112133266800_R85","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28528-w","article-title":"Structural basis for SARS-CoV-2 delta variant recognition of ACE2 receptor and broadly neutralizing antibodies","volume":"13","author":"Wang","year":"2022","journal-title":"Nat Commun"},{"key":"2025071112133266800_R86","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27350-0","article-title":"Conformational dynamics of the beta and kappa SARS-CoV-2 spike proteins and their complexes with ACE2 receptor revealed by cryo-EM","volume":"12","author":"Wang","year":"2021","journal-title":"Nat Commun"},{"key":"2025071112133266800_R87","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1126\/science.abb9983","article-title":"Site-specific glycan analysis of the SARS-CoV-2 spike","volume":"369","author":"Watanabe","year":"2020","journal-title":"Science"},{"key":"2025071112133266800_R88","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.chom.2020.11.012","article-title":"D614G spike mutation increases SARS-CoV-2 susceptibility to neutralization","volume":"29","author":"Weissman","year":"2021","journal-title":"Cell Host Microbe"},{"key":"2025071112133266800_R89","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1038\/s41564-022-01143-7","article-title":"SARS-COV-2 omicron is an immune escape variant with an altered cell entry pathway","volume":"7","author":"Willett","year":"2022","journal-title":"Nat Microbiol"},{"key":"2025071112133266800_R90","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","article-title":"A new coronavirus associated with human respiratory disease in China","volume":"579","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"2025071112133266800_R91","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2023.102664","article-title":"Cryo-EM and cryo-ET of the spike, virion, and antibody neutralization of SARS-CoV-2 and VOCs","volume":"82","author":"Xu","year":"2023","journal-title":"Curr Opin Struct Biol"},{"key":"2025071112133266800_R92","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/s41586-023-06753-7","article-title":"Repeated omicron exposures override ancestral SARS-CoV-2 immune imprinting","volume":"625","author":"Yisimayi","year":"2024","journal-title":"Nature"},{"key":"2025071112133266800_R93","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1126\/science.abh1139","article-title":"Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants","volume":"373","author":"Yuan","year":"2021","journal-title":"Science"},{"key":"2025071112133266800_R94","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02728-4","article-title":"Ten emerging SARS-CoV-2 spike variants exhibit variable infectivity, animal tropism, and antibody neutralization","volume":"4","author":"Zhang","year":"2021","journal-title":"Commun Biol"},{"key":"2025071112133266800_R95","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/s41422-021-00600-y","article-title":"Loss of spike N370 glycosylation as an important evolutionary event for the enhanced infectivity of SARS-CoV-2","volume":"32","author":"Zhang","year":"2022","journal-title":"Cell Res"},{"key":"2025071112133266800_R96","doi-asserted-by":"publisher","first-page":"e00822","DOI":"10.1128\/jvi.00822-23","article-title":"Structural evolution of SARS-CoV-2 omicron in human receptor recognition","volume":"97","author":"Zhang","year":"2023","journal-title":"J Virol"},{"key":"2025071112133266800_R97","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32665-7","article-title":"Omicron SARS-CoV-2 mutations stabilize spike up-RBD conformation and lead to a non-RBM-binding monoclonal antibody escape","volume":"13","author":"Zhao","year":"2022","journal-title":"Nat Commun"},{"key":"2025071112133266800_R98","doi-asserted-by":"publisher","first-page":"e03120","DOI":"10.1128\/spectrum.03120-22","article-title":"Characterization and function of glycans on the spike proteins of SARS-CoV-2 variants of concern","volume":"10","author":"Zheng","year":"2022","journal-title":"Microbiol Spectr"},{"key":"2025071112133266800_R99","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"}],"container-title":["Virus Evolution"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ve\/advance-article-pdf\/doi\/10.1093\/ve\/veaf027\/63463494\/veaf027.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ve\/article-pdf\/11\/1\/veaf027\/63463494\/veaf027.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ve\/article-pdf\/11\/1\/veaf027\/63463494\/veaf027.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T16:13:40Z","timestamp":1752250420000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ve\/article\/doi\/10.1093\/ve\/veaf027\/8159764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":99,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,6,11]]}},"URL":"https:\/\/doi.org\/10.1093\/ve\/veaf027","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.12.06.627164","asserted-by":"object"}]},"ISSN":["2057-1577"],"issn-type":[{"value":"2057-1577","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025]]},"published":{"date-parts":[[2025]]},"article-number":"veaf027"}}