{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:33:09Z","timestamp":1785198789620,"version":"3.55.0"},"reference-count":85,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T00:00:00Z","timestamp":1739836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses an ongoing threat to the efficacy of vaccines and therapeutic antibodies. Mutations predominantly affect the receptor-binding domain (RBD) of the spike protein, which mediates viral entry. The RBD is also a major target of monoclonal antibodies that were authorised for use during the pandemic. In this study, an in silico approach was used to investigate the mutational landscape of SARS-CoV-2 RBD variants, including currently circulating Omicron subvariants. A total of 40 single-point mutations were assessed for their potential effect on protein stability and dynamics. Destabilising effects were predicted for mutations such as L455S and F456L, while stabilising effects were predicted for mutations such as R346T. Conformational B-cell epitope predictions were subsequently performed for wild-type (WT) and variant RBDs. Mutations from SARS-CoV-2 variants were located within the predicted epitope residues and the epitope regions were found to correspond to the sites targeted by therapeutic antibodies. Furthermore, homology models of the RBD of SARS-CoV-2 variants were generated and were utilised for protein\u2013antibody docking. The binding characteristics of 10 monoclonal antibodies against WT and 14 SARS-CoV-2 variants were evaluated. Through evaluating the binding affinities, interactions, and energy contributions of RBD residues, mutations that were contributing to viral evasion were identified. The findings from this study provide insight into the structural and molecular mechanisms underlying neutralising antibody evasion. Future antibody development could focus on broadly neutralising antibodies, engineering antibodies with enhanced binding affinity, and targeting spike protein regions beyond the RBD.<\/jats:p>","DOI":"10.3390\/biom15020301","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T06:41:12Z","timestamp":1739860872000},"page":"301","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Epimaps of the SARS-CoV-2 Receptor-Binding Domain Mutational Landscape: Insights into Protein Stability, Epitope Prediction, and Antibody Binding"],"prefix":"10.3390","volume":"15","author":[{"given":"Eleni","family":"Pitsillou","sequence":"first","affiliation":[{"name":"Epigenomic Medicine Laboratory at prospED Polytechnic, Carlton, VIC 3053, Australia"},{"name":"School of Science, STEM College, RMIT University, Melbourne, VIC 3001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7968-7375","authenticated-orcid":false,"given":"Assam","family":"El-Osta","sequence":"additional","affiliation":[{"name":"Epigenetics in Human Health and Disease Program, Baker Heart and Diabetes Institute, 75 Commercial Road, Prahran, VIC 3004, Australia"},{"name":"Baker Department of Cardiometabolic Health, The University of Melbourne, Parkville, VIC 3010, Australia"},{"name":"Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia"},{"name":"Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, China"},{"name":"Hong Kong Institute of Diabetes and Obesity, Prince of Wales Hospital, The Chinese University of Hong Kong, 3\/F Lui Che Woo Clinical Sciences Building, 30\u201332 Ngan Shing Street, Sha Tin, Hong Kong SAR, China"},{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, China"},{"name":"Biomedical Laboratory Science, Department of Technology, Faculty of Health, University College Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3569-2951","authenticated-orcid":false,"given":"Andrew","family":"Hung","sequence":"additional","affiliation":[{"name":"School of Science, STEM College, RMIT University, Melbourne, VIC 3001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9967-1546","authenticated-orcid":false,"given":"Tom C.","family":"Karagiannis","sequence":"additional","affiliation":[{"name":"Epigenomic Medicine Laboratory at prospED Polytechnic, Carlton, VIC 3053, Australia"},{"name":"Epigenetics in Human Health and Disease Program, Baker Heart and Diabetes Institute, 75 Commercial Road, Prahran, VIC 3004, Australia"},{"name":"Baker Department of Cardiometabolic Health, The University of Melbourne, Parkville, VIC 3010, Australia"},{"name":"Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-2438-7_1","article-title":"Coronaviruses: An overview of their replication and pathogenesis","volume":"1282","author":"Fehr","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41392-020-0190-2","article-title":"Overview of lethal human coronaviruses","volume":"5","author":"Chen","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.4103\/jfmpc.jfmpc_839_21","article-title":"SARS, MERS and CoVID-19: An overview and comparison of clinical, laboratory and radiological features","volume":"11","author":"Pustake","year":"2022","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.cmi.2020.03.026","article-title":"COVID-19, SARS and MERS: Are they closely related?","volume":"26","author":"Petrosillo","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s11427-021-1964-4","article-title":"Overview of SARS-CoV-2 genome-encoded proteins","volume":"65","author":"Bai","year":"2022","journal-title":"Sci. China Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1038\/s41401-021-00851-w","article-title":"Structure genomics of SARS-CoV-2 and its Omicron variant: Drug design templates for COVID-19","volume":"43","author":"Wu","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","article-title":"Mechanisms of SARS-CoV-2 entry into cells","volume":"23","author":"Jackson","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/s41401-020-0485-4","article-title":"Structural and functional properties of SARS-CoV-2 spike protein: Potential antivirus drug development for COVID-19","volume":"41","author":"Huang","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/s41586-020-2179-y","article-title":"Structural basis of receptor recognition by SARS-CoV-2","volume":"581","author":"Shang","year":"2020","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41586-020-2180-5","article-title":"Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor","volume":"581","author":"Lan","year":"2020","journal-title":"Nature"},{"key":"ref_11","unstructured":"Hodcroft, E.B. (2025, January 02). CoVariants: SARS-CoV-2 Mutations and Variants of Interest. Available online: https:\/\/covariants.org\/."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/s41592-023-01769-3","article-title":"Outbreak.info genomic reports: Scalable and dynamic surveillance of SARS-CoV-2 variants and mutations","volume":"20","author":"Gangavarapu","year":"2023","journal-title":"Nat. Methods"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Shah, M., and Woo, H.G. (2021). Omicron: A Heavily Mutated SARS-CoV-2 Variant Exhibits Stronger Binding to ACE2 and Potently Escapes Approved COVID-19 Therapeutic Antibodies. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.830527"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Andre, M., Lau, L.S., Pokharel, M.D., Ramelow, J., Owens, F., Souchak, J., Akkaoui, J., Ales, E., Brown, H., and Shil, R. (2023). From Alpha to Omicron: How Different Variants of Concern of the SARS-Coronavirus-2 Impacted the World. Biology, 12.","DOI":"10.3390\/biology12091267"},{"key":"ref_15","unstructured":"World Health Organization (2024, December 30). Historical Working Definitions and Primary Actions for SARS-CoV-2 Variants. Available online: https:\/\/www.who.int\/publications\/m\/item\/historical-working-definitions-and-primary-actions-for-sars-cov-2-variants."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s41586-022-04474-x","article-title":"Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity","volume":"603","author":"Meng","year":"2022","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/s41586-022-04462-1","article-title":"Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant","volume":"603","author":"Suzuki","year":"2022","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/s41564-023-01588-4","article-title":"Evolution of enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants","volume":"9","author":"Reuschl","year":"2024","journal-title":"Nat. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Cui, L., Li, T., Xue, W., Zhang, S., Wang, H., Liu, H., Gu, Y., Xia, N., and Li, S. (2024). Comprehensive Overview of Broadly Neutralizing Antibodies against SARS-CoV-2 Variants. Viruses, 16.","DOI":"10.20944\/preprints202404.0708.v1"},{"key":"ref_20","doi-asserted-by":"crossref","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":"ref_21","doi-asserted-by":"crossref","unstructured":"Singh, D.D., Parveen, A., and Yadav, D.K. (2021). SARS-CoV-2: Emergence of New Variants and Effectiveness of Vaccines. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.777212"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_23","unstructured":"Schr\u00f6dinger LLC (2015). The PyMOL Molecular Graphics System, Version 1.8."},{"key":"ref_24","unstructured":"Schr\u00f6dinger LLC (2022). Schr\u00f6dinger Release 2022-2: Maestro, Schr\u00f6dinger LLC."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","article-title":"Comparative protein modelling by satisfaction of spatial restraints","volume":"234","author":"Sali","year":"1993","journal-title":"J. Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ovchynnykova, O., Kapusta, K., Sizochenko, N., Sukhyy, K.M., Kolodziejczyk, W., Hill, G.A., and Saloni, J. (2022). Homology Modeling and Molecular Dynamics-Driven Search for Natural Inhibitors That Universally Target Receptor-Binding Domain of Spike Glycoprotein in SARS-CoV-2 Variants. Molecules, 27.","DOI":"10.3390\/molecules27217336"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Li, L., Gao, M., Li, J., Xie, X., Zhao, H., Wang, Y., Xu, X., Zu, S., Chen, C., and Wan, D. (2023). Identification of an immunogenic epitope and protective antibody against the furin cleavage site of SARS-CoV-2. EBioMedicine, 87.","DOI":"10.1016\/j.ebiom.2022.104401"},{"key":"ref_29","first-page":"610","article-title":"Analyzing the interaction of human ACE2 and RBD of spike protein of SARS-CoV-2 in perspective of Omicron variant","volume":"21","author":"Samanta","year":"2022","journal-title":"Excli J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1110\/ps.062416606","article-title":"Statistical potential for assessment and prediction of protein structures","volume":"15","author":"Shen","year":"2006","journal-title":"Protein Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1126\/science.abd0827","article-title":"Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail","volume":"369","author":"Hansen","year":"2020","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1038\/s41564-021-00972-2","article-title":"Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail","volume":"6","author":"Dong","year":"2021","journal-title":"Nat. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Jones, B.E., Brown-Augsburger, P.L., Corbett, K.S., Westendorf, K., Davies, J., Cujec, T.P., Wiethoff, C.M., Blackbourne, J.L., Heinz, B.A., and Foster, D. (2021). The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci. Transl. Med., 13.","DOI":"10.1126\/scitranslmed.abf1906"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41586-020-2381-y","article-title":"A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2","volume":"584","author":"Shi","year":"2020","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"110812","DOI":"10.1016\/j.celrep.2022.110812","article-title":"LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants","volume":"39","author":"Westendorf","year":"2022","journal-title":"Cell Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41586-021-03807-6","article-title":"SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape","volume":"597","author":"Starr","year":"2021","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/s41467-020-20602-5","article-title":"A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein","volume":"12","author":"Kim","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/s41467-023-36295-5","article-title":"Broadly neutralizing SARS-CoV-2 antibodies through epitope-based selection from convalescent patients","volume":"14","author":"Rouet","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.jmb.2007.05.022","article-title":"Inference of Macromolecular Assemblies from Crystalline State","volume":"372","author":"Krissinel","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1002\/elps.1150181505","article-title":"SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling","volume":"18","author":"Guex","year":"1997","journal-title":"Electrophoresis"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5107","DOI":"10.1093\/bioinformatics\/btaa644","article-title":"proABC-2: PRediction of AntiBody contacts v2 and its application to information-driven docking","volume":"36","author":"Ambrosetti","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e4792","DOI":"10.1002\/pro.4792","article-title":"UCSF ChimeraX: Tools for structure building and analysis","volume":"32","author":"Meng","year":"2023","journal-title":"Protein Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0010-4655(95)00042-E","article-title":"GROMACS: A message-passing parallel molecular dynamics implementation","volume":"91","author":"Berendsen","year":"1995","journal-title":"Comput. Phys. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1021\/ct900549r","article-title":"Implementation of the CHARMM Force Field in GROMACS: Analysis of Protein Stability Effects from Correction Maps, Virtual Interaction Sites, and Water Models","volume":"6","author":"Bjelkmar","year":"2010","journal-title":"J. Chem. Theory Comput."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10096","DOI":"10.1063\/1.1808117","article-title":"A modified TIP3P water potential for simulation with Ewald summation","volume":"121","author":"Price","year":"2004","journal-title":"J. Chem. Phys."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Pitsillou, E., Liang, J.J., Kino, N., Lockwood, J.L., Hung, A., El-Osta, A., AbuMaziad, A.S., and Karagiannis, T.C. (2024). An In Silico Investigation of the Pathogenic G151R G Protein-Gated Inwardly Rectifying K+ Channel 4 Variant to Identify Small Molecule Modulators. Biology, 13.","DOI":"10.3390\/biology13120992"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Pitsillou, E., Liang, J.J., Beh, R.C., Hung, A., and Karagiannis, T.C. (2022). Molecular dynamics simulations highlight the altered binding landscape at the spike-ACE2 interface between the Delta and Omicron variants compared to the SARS-CoV-2 original strain. Comput. Biol. Med., 149.","DOI":"10.1016\/j.compbiomed.2022.106035"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Liang, J., Pitsillou, E., Karagiannis, C., Darmawan, K.K., Ng, K., Hung, A., and Karagiannis, T.C. (2020). Interaction of the prototypical \u03b1-ketoamide inhibitor with the SARS-CoV-2 main protease active site in silico: Molecular dynamic simulations highlight the stability of the ligand-protein complex. Comput. Biol. Chem., 87.","DOI":"10.1016\/j.compbiolchem.2020.107292"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Laskowski, R.A., MacArthur, M.W., and Thornton, J.M. (2012). PROCHECK: Validation of protein-structure coordinates. International Tables for Crystallography, Wiley.","DOI":"10.1107\/97809553602060000882"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1093\/bioinformatics\/btz828","article-title":"QMEANDisCo\u2014Distance constraints applied on model quality estimation","volume":"36","author":"Studer","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1038\/s41596-024-01011-0","article-title":"The HADDOCK2.4 web server for integrative modeling of biomolecular complexes","volume":"19","author":"Honorato","year":"2024","journal-title":"Nat. Protoc."},{"key":"ref_53","unstructured":"Bonvin Lab (2024, October 05). HADDOCK2.4 Antibody\u2014Antigen Tutorial Using PDB-Tools Webserver. Available online: https:\/\/www.bonvinlab.org\/education\/HADDOCK24\/HADDOCK24-antibody-antigen\/#scenario-2-a-loose-definition-of-the-epitope-is-known."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/prot.10393","article-title":"Assessment of blind predictions of protein\u2013protein interactions: Current status of docking methods","volume":"52","author":"Leplae","year":"2003","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1093\/bioinformatics\/btz884","article-title":"pyDockEneRes: Per-residue decomposition of protein\u2013protein docking energy","volume":"36","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"W122","DOI":"10.1093\/nar\/gkad472","article-title":"DDMut: Predicting effects of mutations on protein stability using deep learning","volume":"51","author":"Zhou","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/pro.3942","article-title":"DynaMut2: Assessing changes in stability and flexibility upon single and multiple point missense mutations","volume":"30","author":"Rodrigues","year":"2021","journal-title":"Protein Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"W533","DOI":"10.1093\/nar\/gkae386","article-title":"SEMA 2.0: Web-platform for B-cell conformational epitopes prediction using artificial intelligence","volume":"52","author":"Ivanisenko","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual molecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."},{"key":"ref_60","unstructured":"World Health Organization (2025, January 02). Tracking SARS-CoV-2 Variants. Available online: https:\/\/www.who.int\/activities\/tracking-SARS-CoV-2-variants."},{"key":"ref_61","doi-asserted-by":"crossref","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":"ref_62","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1016\/j.cell.2022.06.023","article-title":"Structural basis of human ACE2 higher binding affinity to currently circulating Omicron SARS-CoV-2 sub-variants BA.2 and BA.1.1","volume":"185","author":"Li","year":"2022","journal-title":"Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1016\/j.chom.2022.09.018","article-title":"Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75","volume":"30","author":"Cao","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/S1473-3099(23)00010-5","article-title":"ACE2 binding and antibody evasion in enhanced transmissibility of XBB.1.5","volume":"23","author":"Yue","year":"2023","journal-title":"Lancet Infect. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e457","DOI":"10.1016\/S1473-3099(23)00573-X","article-title":"Antigenicity and infectivity characterisation of SARS-CoV-2 BA.2.86","volume":"23","author":"Yang","year":"2023","journal-title":"Lancet Infect. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S1473-3099(23)00278-5","article-title":"Virological characteristics of the SARS-CoV-2 omicron XBB.1.16 variant","volume":"23","author":"Yamasoba","year":"2023","journal-title":"Lancet Infect. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e70","DOI":"10.1016\/S1473-3099(23)00744-2","article-title":"Fast evolution of SARS-CoV-2 BA.2.86 to JN.1 under heavy immune pressure","volume":"24","author":"Yang","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2402880","DOI":"10.1080\/22221751.2024.2402880","article-title":"Recurrent SARS-CoV-2 spike mutations confer growth advantages to select JN.1 sublineages","volume":"13","author":"Wang","year":"2024","journal-title":"Emerg. Microbes Infect."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Rodrigues, C.H.M., Portelli, S., and Ascher, D.B. (2024). Exploring the effects of missense mutations on protein thermodynamics through structure-based approaches: Findings from the CAGI6 challenges. Hum. Genet.","DOI":"10.1007\/s00439-023-02623-4"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Jacob, J.J., Vasudevan, K., Pragasam, A.K., Gunasekaran, K., Veeraraghavan, B., and Mutreja, A. (2021). Evolutionary Tracking of SARS-CoV-2 Genetic Variants Highlights an Intricate Balance of Stabilizing and Destabilizing Mutations. mBio, 12.","DOI":"10.1128\/mBio.01188-21"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.ijbiomac.2022.07.254","article-title":"Omicron (B.1.1.529)\u2014A new heavily mutated variant: Mapped location and probable properties of its mutations with an emphasis on S-glycoprotein","volume":"219","author":"Chakraborty","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4958","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":"ref_73","unstructured":"U.S. Food and Drug Administration (2024, December 23). Emergency Use Authorization\u2014Archived Information, Available online: https:\/\/www.fda.gov\/emergency-preparedness-and-response\/mcm-legal-regulatory-and-policy-framework\/emergency-use-authorization-archived-information#covid19."},{"key":"ref_74","unstructured":"Therapeutic Goods Administration (2024, December 23). Update on Effectiveness of Monoclonal Antibodies Against COVID Variants, Available online: https:\/\/www.tga.gov.au\/news\/news\/update-effectiveness-monoclonal-antibodies-against-covid-variants#:~:text=Monoclonal%20antibodies%20targeting%20the%20SARS,spike%20protein%20on%20its%20surface."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4196","DOI":"10.1038\/s41467-021-24435-8","article-title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","volume":"12","author":"Greaney","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1021\/acs.jpcb.2c00708","article-title":"Cocktail of REGN Antibodies Binds More Strongly to SARS-CoV-2 Than Its Components, but the Omicron Variant Reduces Its Neutralizing Ability","volume":"126","author":"Nguyen","year":"2022","journal-title":"J. Phys. Chem. B"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Fung, K.M., Lai, S.J., Lin, T.L., and Tseng, T.S. (2022). Antigen-Antibody Complex-Guided Exploration of the Hotspots Conferring the Immune-Escaping Ability of the SARS-CoV-2 RBD. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.797132"},{"key":"ref_78","doi-asserted-by":"crossref","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":"ref_79","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41586-020-2349-y","article-title":"Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody","volume":"583","author":"Pinto","year":"2020","journal-title":"Nature"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Focosi, D., Casadevall, A., Franchini, M., and Maggi, F. (2024). Sotrovimab: A Review of Its Efficacy against SARS-CoV-2 Variants. Viruses, 16.","DOI":"10.3390\/v16020217"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"100991","DOI":"10.1016\/j.xcrm.2023.100991","article-title":"An updated atlas of antibody evasion by SARS-CoV-2 Omicron sub-variants including BQ.1.1 and XBB","volume":"4","author":"He","year":"2023","journal-title":"Cell Rep. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/j.str.2024.06.012","article-title":"Spike structures, receptor binding, and immune escape of recently circulating SARS-CoV-2 Omicron BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 sub-variants","volume":"32","author":"Li","year":"2024","journal-title":"Structure"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.cell.2022.12.018","article-title":"Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants","volume":"186","author":"Wang","year":"2023","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3426","DOI":"10.1016\/j.cell.2021.04.025","article-title":"Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant","volume":"184","author":"Deng","year":"2021","journal-title":"Cell"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Wilhelm, A., Toptan, T., Pallas, C., Wolf, T., Goetsch, U., Gottschalk, R., Vehreschild, M., Ciesek, S., and Widera, M. (2021). Antibody-Mediated Neutralization of Authentic SARS-CoV-2 B.1.617 Variants Harboring L452R and T478K\/E484Q. Viruses, 13.","DOI":"10.1101\/2021.08.09.21261704"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/2\/301\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:36:50Z","timestamp":1760027810000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/2\/301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,18]]},"references-count":85,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["biom15020301"],"URL":"https:\/\/doi.org\/10.3390\/biom15020301","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,18]]}}}