{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:57:59Z","timestamp":1787497079228,"version":"build-2736575974"},"reference-count":143,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kay Family Foundation","award":["A20-0032"],"award-info":[{"award-number":["A20-0032"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>A significant body of experimental structures of SARS-CoV-2 spike trimers for the BA.1 and BA.2 variants revealed a considerable plasticity of the spike protein and the emergence of druggable binding pockets. Understanding the interplay of conformational dynamics changes induced by the Omicron variants and the identification of cryptic dynamic binding pockets in the S protein is of paramount importance as exploring broad-spectrum antiviral agents to combat the emerging variants is imperative. In the current study, we explore conformational landscapes and characterize the universe of binding pockets in multiple open and closed functional spike states of the BA.1 and BA.2 Omicron variants. By using a combination of atomistic simulations, a dynamics network analysis, and an allostery-guided network screening of binding pockets in the conformational ensembles of the BA.1 and BA.2 spike conformations, we identified all experimentally known allosteric sites and discovered significant variant-specific differences in the distribution of binding sites in the BA.1 and BA.2 trimers. This study provided a structural characterization of the predicted cryptic pockets and captured the experimentally known allosteric sites, revealing the critical role of conformational plasticity in modulating the distribution and cross-talk between functional binding sites. We found that mutational and dynamic changes in the BA.1 variant can induce the remodeling and stabilization of a known druggable pocket in the N-terminal domain, while this pocket is drastically altered and may no longer be available for ligand binding in the BA.2 variant. Our results predicted the experimentally known allosteric site in the receptor-binding domain that remains stable and ranks as the most favorable site in the conformational ensembles of the BA.2 variant but could become fragmented and less probable in BA.1 conformations. We also uncovered several cryptic pockets formed at the inter-domain and inter-protomer interface, including functional regions of the S2 subunit and stem helix region, which are consistent with the known role of pocket residues in modulating conformational transitions and antibody recognition. The results of this study are particularly significant for understanding the dynamic and network features of the universe of available binding pockets in spike proteins, as well as the effects of the Omicron-variant-specific modulation of preferential druggable pockets. The exploration of predicted druggable sites can present a new and previously underappreciated opportunity for therapeutic interventions for Omicron variants through the conformation-selective and variant-specific targeting of functional sites involved in allosteric changes.<\/jats:p>","DOI":"10.3390\/v15102009","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T07:38:46Z","timestamp":1695800326000},"page":"2009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Exploring Conformational Landscapes and Cryptic Binding Pockets in Distinct Functional States of the SARS-CoV-2 Omicron BA.1 and BA.2 Trimers: Mutation-Induced Modulation of Protein Dynamics and Network-Guided Prediction of Variant-Specific Allosteric Binding Sites"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4507-4471","authenticated-orcid":false,"given":"Gennady","family":"Verkhivker","sequence":"first","affiliation":[{"name":"Keck Center for Science and Engineering, Graduate Program in Computational and Data Sciences, Schmid College of Science and Technology, Chapman University, Orange, CA 92866, USA"},{"name":"Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Irvine, CA 92618, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3504-6386","authenticated-orcid":false,"given":"Mohammed","family":"Alshahrani","sequence":"additional","affiliation":[{"name":"Keck Center for Science and Engineering, Graduate Program in Computational and Data Sciences, Schmid College of Science and Technology, Chapman University, Orange, CA 92866, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Gupta","sequence":"additional","affiliation":[{"name":"Keck Center for Science and Engineering, Graduate Program in Computational and Data Sciences, Schmid College of Science and Technology, Chapman University, Orange, CA 92866, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/s41423-020-0400-4","article-title":"Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: Implication for development of RBD protein as a viral attachment inhibitor and vaccine","volume":"17","author":"Tai","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.cell.2020.03.045","article-title":"Structural and functional basis of SARS-CoV-2 entry by using human ACE2","volume":"181","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","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":"ref_4","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.abb2507","article-title":"Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation","volume":"367","author":"Wrapp","year":"2020","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Papageorgiou, A.C., and Mohsin, I. (2020). The SARS-CoV-2 Spike Glycoprotein as a Drug and Vaccine Target: Structural Insights into Its Complexes with ACE2 and Antibodies. Cells, 9.","DOI":"10.3390\/cells9112343"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1126\/science.abd0826","article-title":"Structure-based design of prefusion-stabilized SARS-CoV-2 spikes","volume":"369","author":"Hsieh","year":"2020","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"108630","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":"ref_8","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/s41594-020-0483-8","article-title":"Structure-guided covalent stabilization of coronavirus spike glycoprotein trimers in the closed conformation","volume":"27","author":"McCallum","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/s41594-020-0478-5","article-title":"A thermostable, closed SARS-CoV-2 spike protein trimer","volume":"27","author":"Xiong","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e0020321","DOI":"10.1128\/JVI.00203-21","article-title":"SARS-CoV-2 Spike Protein Stabilized in the Closed State Induces Potent Neutralizing Responses","volume":"95","author":"Carnell","year":"2021","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1126\/science.abg4493","article-title":"The emerging plasticity of SARS-CoV-2","volume":"371","author":"McCormick","year":"2021","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ghimire, D., Han, Y., and Lu, M. (2022). Structural Plasticity and Immune Evasion of SARS-CoV-2 Spike Variants. Viruses, 14.","DOI":"10.3390\/v14061255"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7345","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":"ref_14","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41586-020-2772-0","article-title":"Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion","volume":"588","author":"Benton","year":"2020","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1126\/science.abd5223","article-title":"In Situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges","volume":"370","author":"Sikora","year":"2020","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.chom.2020.11.001","article-title":"Real-time conformational dynamics of SARS-CoV-2 spikes on virus particles","volume":"28","author":"Lu","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Yang, Z., Han, Y., Ding, S., Shi, W., Zhou, T., Finzi, A., Kwong, P.D., Mothes, W., and Lu, M. (2022). SARS-CoV-2 Variants Increase Kinetic Stability of Open Spike Conformations as an Evolutionary Strategy. mBio, 13.","DOI":"10.1128\/mbio.03227-21"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e75433","DOI":"10.7554\/eLife.75433","article-title":"Conformational dynamics and allosteric modulation of the SARS-CoV-2 spike","volume":"11","author":"Li","year":"2022","journal-title":"eLife"},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/s41467-022-28324-6","article-title":"Structural and biochemical rationale for enhanced spike protein fitness in delta and kappa SARS-CoV-2 variants","volume":"13","author":"Saville","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"871","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":"ref_22","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1126\/science.abl9463","article-title":"Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant","volume":"374","author":"Zhang","year":"2021","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1126\/science.abn7760","article-title":"SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein-ACE2 complex","volume":"375","author":"Mannar","year":"2022","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","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":"ref_25","doi-asserted-by":"crossref","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":"ref_26","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1126\/science.abn8863","article-title":"Structures of the Omicron Spike trimer with ACE2 and an anti-Omicron antibody","volume":"375","author":"Yin","year":"2022","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","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":"ref_28","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.cell.2022.01.019","article-title":"Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron","volume":"185","author":"Cui","year":"2022","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"eabn8897","DOI":"10.1126\/science.abn8897","article-title":"Structural basis for potent antibody neutralization of SARS-CoV-2 variants including B.1.1.529","volume":"376","author":"Zhou","year":"2022","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"110770","DOI":"10.1016\/j.celrep.2022.110770","article-title":"Structures of Omicron Spike Complexes and Implications for Neutralizing Antibody Development","volume":"39","author":"Guo","year":"2022","journal-title":"Cell Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"111009","DOI":"10.1016\/j.celrep.2022.111009","article-title":"Cryo-EM Structures of SARS-CoV-2 Omicron BA.2 Spike","volume":"39","author":"Stalls","year":"2022","journal-title":"Cell Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41392-022-00914-2","article-title":"Characterization of SARS-CoV-2 Omicron Spike RBD Reveals Significantly Decreased Stability, Severe Evasion of Neutralizing-Antibody Recognition but Unaffected Engagement by Decoy ACE2 Modified for Enhanced RBD Binding","volume":"7","author":"Lin","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_33","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_34","doi-asserted-by":"crossref","first-page":"110428","DOI":"10.1016\/j.celrep.2022.110428","article-title":"Cryo-EM Structure of the SARS-CoV-2 Omicron Spike","volume":"38","author":"Cerutti","year":"2022","journal-title":"Cell Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1038\/s41467-022-28882-9","article-title":"Cryo-EM Structure of a SARS-CoV-2 Omicron Spike Protein Ectodomain","volume":"13","author":"Ye","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/s41422-022-00672-4","article-title":"Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.2 variant compared to BA.1 and their possible mouse origins","volume":"32","author":"Xu","year":"2022","journal-title":"Cell Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"110729","DOI":"10.1016\/j.celrep.2022.110729","article-title":"Structural and Functional Impact by SARS-CoV-2 Omicron Spike Mutations","volume":"39","author":"Zhang","year":"2022","journal-title":"Cell Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/s41594-023-01023-6","article-title":"Structural and Functional Characteristics of the SARS-CoV-2 Omicron Subvariant BA.2 Spike Protein","volume":"30","author":"Zhang","year":"2023","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","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":"ref_40","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/s41594-022-00735-5","article-title":"The SARS-CoV-2 Spike Reversibly Samples an Open-Trimer Conformation Exposing Novel Epitopes","volume":"29","author":"Costello","year":"2022","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1421","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":"ref_42","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.chom.2021.03.005","article-title":"Potent SARS-CoV-2 Neutralizing Antibodies Directed against Spike N-Terminal Domain Target a Single Supersite","volume":"29","author":"Cerutti","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/s41586-022-04594-4","article-title":"Antibody Evasion Properties of SARS-CoV-2 Omicron Sublineages","volume":"604","author":"Iketani","year":"2022","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1016\/j.immuni.2022.06.005","article-title":"Atlas of Currently Available Human Neutralizing Antibodies against SARS-CoV-2 and Escape by Omicron Sub-Variants BA.1\/BA.1.1\/BA.2\/BA.3","volume":"55","author":"Huang","year":"2022","journal-title":"Immunity"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"eabo3153","DOI":"10.1126\/sciadv.abo3153","article-title":"Intermediates in SARS-CoV-2 Spike\u2013Mediated Cell Entry","volume":"8","author":"Marcink","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1021\/acs.accounts.9b00613","article-title":"Investigating Cryptic Binding Sites by Molecular Dynamics Simulations","volume":"53","author":"Kuzmanic","year":"2020","journal-title":"Acc. Chem. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"E3416","DOI":"10.1073\/pnas.1711490115","article-title":"Exploring the Structural Origins of Cryptic Sites on Proteins","volume":"115","author":"Beglov","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.jmb.2016.01.029","article-title":"CryptoSite: Expanding the Druggable Proteome by Characterization and Prediction of Cryptic Binding Sites","volume":"428","author":"Cimermancic","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1126\/science.abb7269","article-title":"A Highly Conserved Cryptic Epitope in the Receptor Binding Domains of SARS-CoV-2 and SARS-CoV","volume":"368","author":"Yuan","year":"2020","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1126\/science.abd3255","article-title":"Free Fatty Acid Binding Pocket in the Locked Structure of SARS-CoV-2 Spike Protein","volume":"370","author":"Toelzer","year":"2020","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1107\/S2059798323000049","article-title":"Cryo-EM Reveals Binding of Linoleic Acid to SARS-CoV-2 Spike Glycoprotein, Suggesting an Antiviral Treatment Strategy","volume":"79","author":"Toelzer","year":"2023","journal-title":"Acta Crystallogr. D Struct. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"eadc9179","DOI":"10.1126\/sciadv.adc9179","article-title":"The Free Fatty Acid\u2013Binding Pocket Is a Conserved Hallmark in Pathogenic \u03b2-Coronavirus Spike Proteins from SARS-CoV to Omicron","volume":"8","author":"Toelzer","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41392-023-01534-0","article-title":"Defining a Highly Conserved Cryptic Epitope for Antibody Recognition of SARS-CoV-2 Variants","volume":"8","author":"Hao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1126\/science.abe1502","article-title":"Structural Analysis of Full-Length SARS-CoV-2 Spike Protein from an Advanced Vaccine Candidate","volume":"370","author":"Bangaru","year":"2020","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"eabg7607","DOI":"10.1126\/sciadv.abg7607","article-title":"SARS-CoV-2 Can Recruit a Heme Metabolite to Evade Antibody Immunity","volume":"7","author":"Rosa","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Altomare, C.G., Adelsberg, D.C., Carreno, J.M., Sapse, I.A., Amanat, F., Ellebedy, A.H., Simon, V., Krammer, F., and Bajic, G. (2022). Structure of a Vaccine-Induced, Germline-Encoded Human Antibody Defines a Neutralizing Epitope on the SARS-CoV-2 Spike N-Terminal Domain. mBio, 13.","DOI":"10.1128\/mbio.03580-21"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Yu, X., Juraszek, J., Rutten, L., Bakkers, M.J.G., Blokland, S., Melchers, J.M., van den Broek, N.J.F., Verwilligen, A.Y.W., Abeywickrema, P., and Vingerhoets, J. (2023). Convergence of Immune Escape Strategies Highlights Plasticity of SARS-CoV-2 Spike. PLoS Pathog., 19.","DOI":"10.1371\/journal.ppat.1011308"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/s41557-021-00758-3","article-title":"A glycan gate controls the opening of the SARS-CoV-2 spike protein","volume":"13","author":"Sztain","year":"2021","journal-title":"Nat. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Sikora, M., von B\u00fclow, S., Blanc, F.E.C., Gecht, M., Covino, R., and Hummer, G. (2021). Computational epitope map of SARS-CoV-2 spike protein. PLoS Comput. Biol., 17.","DOI":"10.1371\/journal.pcbi.1008790"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Pang, Y.T., Acharya, A., Lynch, D.L., Pavlova, A., and Gumbart, J.C. (2022). SARS-CoV-2 Spike Opening Dynamics and Energetics Reveal the Individual Roles of Glycans and Their Collective Impact. Commun. Biol., 5.","DOI":"10.1038\/s42003-022-04138-6"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"eabe5575","DOI":"10.1126\/sciadv.abe5575","article-title":"Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM","volume":"7","author":"Xu","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s41557-021-00707-0","article-title":"SARS-CoV-2 simulations go exascale to predict dramatic spike opening and cryptic pockets across the proteome","volume":"13","author":"Zimmerman","year":"2021","journal-title":"Nat. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.bpj.2021.01.012","article-title":"Elucidation of Interactions Regulating Conformational Stability and Dynamics of SARS-CoV-2 S-Protein","volume":"120","author":"Mori","year":"2021","journal-title":"Biophys. J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e75720","DOI":"10.7554\/eLife.75720","article-title":"The inherent flexibility of receptor binding domains in SARS-CoV-2 spike protein","volume":"11","author":"Dokainish","year":"2022","journal-title":"eLife"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"9168","DOI":"10.1039\/D1SC00244A","article-title":"Determination of intermediate state structures in the opening pathway of SARS-CoV-2 spike using cryo-electron microscopy","volume":"12","author":"Brotzakis","year":"2021","journal-title":"Chem. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1021\/acs.jpcb.0c10637","article-title":"Dynamic Network Modeling of Allosteric Interactions and Communication Pathways in the SARS-CoV-2 Spike Trimer Mutants: Differential Modulation of Conformational Landscapes and Signal Transmission via Cascades of Regulatory Switches","volume":"125","author":"Verkhivker","year":"2021","journal-title":"J. Phys. Chem. B"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4596","DOI":"10.1021\/acs.jpcb.1c00395","article-title":"Integrated Biophysical Modeling of the SARS-CoV-2 Spike Protein Binding and Allosteric Interactions with Antibodies","volume":"125","author":"Verkhivker","year":"2021","journal-title":"J. Phys. Chem. B"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4578","DOI":"10.1021\/acs.jctc.1c00372","article-title":"Dynamic Profiling of Binding and Allosteric Propensities of the SARS-CoV-2 Spike Protein with Different Classes of Antibodies: Mutational and Perturbation-Based Scanning Reveals the Allosteric Duality of Functionally Adaptable Hotspots","volume":"17","author":"Verkhivker","year":"2021","journal-title":"J. Chem. Theory Comput."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1021\/acs.biochem.1c00139","article-title":"Comparative Perturbation-Based Modeling of the SARS-CoV-2 Spike Protein Binding with Host Receptor and Neutralizing Antibodies: Structurally Adaptable Allosteric Communication Hotspots Define Spike Sites Targeted by Global Circulating Mutations","volume":"60","author":"Verkhivker","year":"2021","journal-title":"Biochemistry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"17723","DOI":"10.1039\/D2CP01893D","article-title":"Frustration-driven allosteric regulation and signal transmission in the SARS-CoV-2 spike omicron trimer structures: A crosstalk of the omicron mutation sites allosterically regulates tradeoffs of protein stability and conformational adaptability","volume":"24","author":"Verkhivker","year":"2022","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.str.2022.05.006","article-title":"Uncovering Cryptic Pockets in the SARS-CoV-2 Spike Glycoprotein","volume":"30","author":"Zuzic","year":"2022","journal-title":"Structure"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1038\/s41467-019-11062-7","article-title":"Cryptic Pocket Formation Underlies Allosteric Modulator Selectivity at Muscarinic GPCRs","volume":"10","author":"Hollingsworth","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3495","DOI":"10.1021\/acs.jcim.1c00140","article-title":"Elucidation of Cryptic and Allosteric Pockets within the SARS-CoV-2 Main Protease","volume":"61","author":"Sztain","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13321-018-0285-8","article-title":"P2Rank: Machine Learning Based Tool for Rapid and Accurate Prediction of Ligand Binding Sites from Protein Structure","volume":"10","author":"Hoksza","year":"2018","journal-title":"J. Cheminform."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"W593","DOI":"10.1093\/nar\/gkac389","article-title":"PrankWeb 3: Accelerated Ligand-Binding Site Predictions for Experimental and Modelled Protein Structures","volume":"50","author":"Jakubec","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Kozlovskii, I., and Popov, P. (2020). Spatiotemporal identification of druggable binding sites using deep learning. Commun. Biol., 3.","DOI":"10.1038\/s42003-020-01350-0"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Xiao, S., Tian, H., and Tao, P. (2022). PASSer2.0: Accurate Prediction of Protein Allosteric Sites Through Automated Machine Learning. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.879251"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"W427","DOI":"10.1093\/nar\/gkad303","article-title":"PASSer: Fast and Accurate Prediction of Protein Allosteric Sites","volume":"51","author":"Tian","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1002\/jcc.27193","article-title":"PASSerRank: Prediction of Allosteric Sites with Learning to Rank","volume":"44","author":"Tian","year":"2023","journal-title":"J. Comput. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4355","DOI":"10.1021\/acs.jctc.2c01189","article-title":"Accelerating Cryptic Pocket Discovery Using AlphaFold","volume":"19","author":"Meller","year":"2023","journal-title":"J. Chem. Theory Comput."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1038\/s41467-023-36699-3","article-title":"Predicting Locations of Cryptic Pockets from Single Protein Structures Using the PocketMiner Graph Neural Network","volume":"14","author":"Meller","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1038\/s41467-022-29927-9","article-title":"A Cryptic Pocket in Ebola VP35 Allosterically Controls RNA Binding","volume":"13","author":"Cruz","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.1038\/s41467-021-23246-1","article-title":"Deep learning the structural determinants of protein biochemical properties by comparing structural ensembles with DiffNets","volume":"12","author":"Ward","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e83602","DOI":"10.7554\/eLife.83602","article-title":"Drug Specificity and Affinity Are Encoded in the Probability of Cryptic Pocket Opening in Myosin Motor Domains","volume":"12","author":"Meller","year":"2023","journal-title":"eLife"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Meller, A., De Oliveira, S., Davtyan, A., Abramyan, T., Bowman, G.R., and van den Bedem, H. (2023). Discovery of a Cryptic Pocket in the AI-Predicted Structure of PPM1D Phosphatase Explains the Binding Site and Potency of Its Allosteric Inhibitors. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1171143"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1016\/j.csbj.2023.03.029","article-title":"Identifying Promising Druggable Binding Sites and Their Flexibility to Target the Receptor-Binding Domain of SARS-CoV-2 Spike Protein","volume":"21","author":"Ghoula","year":"2023","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"660490","DOI":"10.3389\/fphar.2021.660490","article-title":"The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models","volume":"12","author":"Davies","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Huang, J., Chan, K.C., and Zhou, R. (2023). Novel Inhibitory Role of Fenofibric Acid by Targeting Cryptic Site on the RBD of SARS-CoV-2. Biomolecules, 13.","DOI":"10.3390\/biom13020359"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"17728","DOI":"10.1021\/acs.jmedchem.1c01695","article-title":"Harnessing Reversed Allosteric Communication: A Novel Strategy for Allosteric Drug Discovery","volume":"64","author":"Fan","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Tee, W.-V., Guarnera, E., and Berezovsky, I.N. (2018). Reversing allosteric communication: From detecting allosteric sites to inducing and tuning targeted allosteric response. PLoS Comput. Biol., 14.","DOI":"10.1371\/journal.pcbi.1006228"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1039\/D0SC05131D","article-title":"Discovery of cryptic allosteric sites using reversed allosteric communication by a combined computational and experimental strategy","volume":"12","author":"Ni","year":"2020","journal-title":"Chem. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Verkhivker, G., Agajanian, S., Kassab, R., and Krishnan, K. (2022). Probing Mechanisms of Binding and Allostery in the SARS-CoV-2 Spike Omicron Variant Complexes with the Host Receptor: Revealing Functional Roles of the Binding Hotspots in Mediating Epistatic Effects and Communication with Allosteric Pockets. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911542"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.1021\/acs.jmedchem.1c00320","article-title":"Probing the Allosteric Inhibition Mechanism of a Spike Protein Using Molecular Dynamics Simulations and Active Compound Identifications","volume":"65","author":"Wang","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"659764","DOI":"10.3389\/fchem.2021.659764","article-title":"Identification of Potential Binding Sites of Sialic Acids on the RBD Domain of SARS-CoV-2 Spike Protein","volume":"9","author":"Li","year":"2021","journal-title":"Front. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s41392-023-01472-x","article-title":"Targetable Elements in SARS-CoV-2 S2 Subunit for the Design of Pan-Coronavirus Fusion Inhibitors and Vaccines","volume":"8","author":"Guo","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e00194-21","DOI":"10.1128\/JVI.00194-21","article-title":"Cryo-Electron Microscopy Structure of S-Trimer, a Subunit Vaccine Candidate for COVID-19","volume":"95","author":"Ma","year":"2021","journal-title":"J. Virol."},{"key":"ref_97","first-page":"D271","article-title":"The RCSB protein data bank: Integrative view of protein, gene and 3D structural information","volume":"45","author":"Rose","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"W719","DOI":"10.1093\/nar\/gkq453","article-title":"WIWS: A protein structure bioinformatics web service collection","volume":"38","author":"Hekkelman","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1021\/ct200133y","article-title":"Improved treatment of ligands and coupling effects in empirical calculation and rationalization of pKa values","volume":"7","author":"Olsson","year":"2011","journal-title":"J. Chem. Theory Comput."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1021\/ct100578z","article-title":"PROPKA3: Consistent treatment of internal and surface residues in empirical pKa predictions","volume":"7","author":"Olsson","year":"2011","journal-title":"J. Chem. Theory Comput."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"W173","DOI":"10.1093\/nar\/gkl113","article-title":"ArchPRED: A template based loop structure prediction server","volume":"34","author":"Zhai","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/prot.22488","article-title":"Improved prediction of protein side-chain conformations with SCWRL4","volume":"77","author":"Krivov","year":"2009","journal-title":"Proteins"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"W406","DOI":"10.1093\/nar\/gkw336","article-title":"3Drefine: An Interactive Web Server for Efficient Protein Structure Refinement","volume":"44","author":"Bhattacharya","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/bs.mie.2016.05.022","article-title":"Bridging Enzymatic Structure Function via Mechanics: A Coarse-Grain Approach","volume":"578","year":"2016","journal-title":"Methods Enzymol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1110\/ps.0239303","article-title":"Protein\u2013protein docking with a reduced protein model accounting for side-chain flexibility","volume":"12","author":"Zacharias","year":"2003","journal-title":"Protein Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1063\/1.436761","article-title":"Brownian dynamics with hydrodynamic interactions","volume":"69","author":"Ermak","year":"1978","journal-title":"J. Chem. Phys."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1063\/1.455218","article-title":"Brownian dynamics simulation of a lipid chain in a membrane bilayer","volume":"89","author":"Pastor","year":"1988","journal-title":"J. Chem. Phys."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1002\/jcc.20906","article-title":"Fast procedure for reconstruction of full-atom protein models from reduced representations","volume":"29","author":"Rotkiewicz","year":"2008","journal-title":"J. Comput. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1093\/bioinformatics\/btv740","article-title":"CG2AA: Backmapping protein coarse-grained structures","volume":"32","author":"Lombardi","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"044130","DOI":"10.1063\/5.0014475","article-title":"Scalable Molecular Dynamics on CPU and GPU Architectures with NAMD","volume":"153","author":"Phillips","year":"2020","journal-title":"J. Chem. Phys."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nmeth.4067","article-title":"CHARMM36m: An improved force field for folded and intrinsically disordered proteins","volume":"14","author":"Huang","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of Simple Potential Functions for Simulating Liquid Water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"5466","DOI":"10.1021\/acs.jpcb.7b11734","article-title":"Biomolecular Simulations under Realistic Macroscopic Salt Conditions","volume":"122","author":"Ross","year":"2018","journal-title":"J. Phys. Chem. B"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"5624","DOI":"10.1021\/acs.jctc.5b00648","article-title":"A Stochastic Algorithm for the Isobaric-Isothermal Ensemble with Ewald Summations for All Long Range Forces","volume":"11","author":"Elber","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1063\/1.467468","article-title":"Constant pressure molecular dynamics algorithms","volume":"101","author":"Martyna","year":"1994","journal-title":"J. Chem. Phys."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"4613","DOI":"10.1063\/1.470648","article-title":"Constant pressure molecular dynamics simulation: The Langevin piston method","volume":"103","author":"Feller","year":"1995","journal-title":"J. Chem. Phys."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"234101","DOI":"10.1063\/1.3149788","article-title":"Langevin thermostat for rigid body dynamics","volume":"130","author":"Davidchack","year":"2009","journal-title":"J. Chem. Phys."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.1016\/j.bpj.2010.08.079","article-title":"Interaction energy based protein structure networks","volume":"99","author":"Vijayabaskar","year":"2010","journal-title":"Biophys. J."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"6620","DOI":"10.1073\/pnas.0810961106","article-title":"Dynamical networks in tRNA:protein complexes","volume":"106","author":"Sethi","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Stetz, G., and Verkhivker, G.M. (2017). Computational analysis of residue interaction networks and coevolutionary relationships in the Hsp70 chaperones: A community-hopping model of allosteric regulation and communication. PLoS Comput. Biol., 13.","DOI":"10.1371\/journal.pcbi.1005299"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"W651","DOI":"10.1093\/nar\/gkac365","article-title":"RING 3.0: Fast Generation of Probabilistic Residue Interaction Networks from Structural Ensembles","volume":"50","author":"Clementel","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_122","unstructured":"Varoquaux, G., Vaught, T., and Millman, J. (2008, January 19\u201324). Exploring network structure, dynamics, and function using NetworkX. Proceedings of the 7th Python in Science Conference (SciPy2008), Pasadena, CA, USA."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"7821","DOI":"10.1073\/pnas.122653799","article-title":"Community Structure in Social and Biological Networks","volume":"99","author":"Girvan","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3362","DOI":"10.1021\/acs.jctc.9b00119","article-title":"Atomistic Modeling of the ABL Kinase Regulation by Allosteric Modulators Using Structural Perturbation Analysis and Community-Based Network Reconstruction of Allosteric Communications","volume":"15","author":"Astl","year":"2019","journal-title":"J. Chem. Theory Comput."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1093\/comnet\/cnv022","article-title":"Detecting Global Bridges in Networks","volume":"4","author":"Jensen","year":"2016","journal-title":"J. Complex Netw."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"W582","DOI":"10.1093\/nar\/gkq383","article-title":"Fpocket: Online Tools for Protein Ensemble Pocket Detection and Tracking","volume":"38","author":"Schmidtke","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_127","unstructured":"Ke, G., Meng, Q., Finley, T., Wang, T., Chen, W., Ma, W., Ye, Q., and Liu, T.-Y. (2017). Advances in Neural Information Processing Systems, Proceedings of the 31st Conference on Neural Information Processing Systems (NIPS 2017), Long Beach, CA, USA, 4\u20139 December 2017, The MIT Press."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Chen, T., and Guestrin, C. (2016, January 13\u201317). Xgboost: A scalable tree boosting system. Proceedings of the 22nd ACM SIGKDD International Conference on Knowledge Discovery and Data Mining, San Francisco, CA, USA.","DOI":"10.1145\/2939672.2939785"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/s12038-007-0089-x","article-title":"Protein Mechanics: A Route from Structure to Function","volume":"32","author":"Lavery","year":"2007","journal-title":"J. Biosci."},{"key":"ref_130","first-page":"229","article-title":"Motions and Mechanics: Investigating Conformational Transitions in Multi-Domain Proteins with Coarse-Grain Simulations","volume":"40","year":"2013","journal-title":"Mol. Simul."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/978-1-62703-658-0_11","article-title":"Principal component analysis: A method for determining the essential dynamics of proteins","volume":"1084","author":"David","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e202200491","DOI":"10.1002\/cphc.202200491","article-title":"On the Uses of PCA to Characterise Molecular Dynamics Simulations of Biological Macromolecules: Basics and Tips for an Effective Use","volume":"24","author":"Palma","year":"2023","journal-title":"ChemPhysChem"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"e82584","DOI":"10.7554\/eLife.82584","article-title":"Timeline of Changes in Spike Conformational Dynamics in Emergent SARS-CoV-2 Variants Reveal Progressive Stabilization of Trimer Stalk with Altered NTD Dynamics","volume":"12","author":"Braet","year":"2023","journal-title":"eLife"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"e63646","DOI":"10.7554\/eLife.63646","article-title":"SARS-CoV-2 S Protein:ACE2 Interaction Reveals Novel Allosteric Targets","volume":"10","author":"Raghuvamsi","year":"2021","journal-title":"eLife"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1021\/acsinfecdis.3c00010","article-title":"hACE2-Induced Allosteric Activation in SARS-CoV versus SARS-CoV-2 Spike Assemblies Revealed by Structural Dynamics","volume":"9","author":"Chen","year":"2023","journal-title":"ACS Infect. Dis."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1016\/j.cell.2021.03.028","article-title":"N-Terminal Domain Antigenic Mapping Reveals a Site of Vulnerability for SARS-CoV-2","volume":"184","author":"McCallum","year":"2021","journal-title":"Cell"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1126\/science.abd4251","article-title":"Distinct conformational states of SARS-CoV-2 spike protein","volume":"369","author":"Cai","year":"2020","journal-title":"Science"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1038\/s41594-020-0479-4","article-title":"Controlling the SARS-CoV-2 spike glycoprotein conformation","volume":"27","author":"Henderson","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1038\/s41467-022-31115-8","article-title":"Anatomy of Omicron BA.1 and BA.2 Neutralizing Antibodies in COVID-19 mRNA Vaccinees","volume":"13","author":"Andreano","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Shoemark, D.K., Oliveira, A.S.F., Davidson, A.D., Berger, I., Schaffitzel, C., and Mulholland, A.J. (2022). Molecular Dynamics of Spike Variants in the Locked Conformation: RBD Interfaces, Fatty Acid Binding and Furin Cleavage Sites. bioRxiv.","DOI":"10.1101\/2022.05.06.490927"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41421-020-0169-8","article-title":"The Anti-Influenza Virus Drug, Arbidol Is an Efficient Inhibitor of SARS-CoV-2 in Vitro","volume":"6","author":"Wang","year":"2020","journal-title":"Cell Discov."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"105998","DOI":"10.1016\/j.ijantimicag.2020.105998","article-title":"Arbidol: A Potential Antiviral Drug for the Treatment of SARS-CoV-2 by Blocking Trimerization of the Spike Glycoprotein","volume":"56","author":"Vankadari","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"e83710","DOI":"10.7554\/eLife.83710","article-title":"Identification of a Conserved S2 Epitope Present on Spike Proteins from All Highly Pathogenic Coronaviruses","volume":"12","author":"Silva","year":"2023","journal-title":"eLife"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/10\/2009\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:59:36Z","timestamp":1760129976000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/10\/2009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,27]]},"references-count":143,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["v15102009"],"URL":"https:\/\/doi.org\/10.3390\/v15102009","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,27]]}}}