{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T12:15:18Z","timestamp":1773404118928,"version":"3.50.1"},"reference-count":73,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T00:00:00Z","timestamp":1675641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NSERC Discovery Grant","award":["RGPIN-2018-04994"],"award-info":[{"award-number":["RGPIN-2018-04994"]}]},{"name":"NSERC Discovery Grant","award":["#RCP-12-002C"],"award-info":[{"award-number":["#RCP-12-002C"]}]},{"name":"Campus Alberta Innovates Program","award":["RGPIN-2018-04994"],"award-info":[{"award-number":["RGPIN-2018-04994"]}]},{"name":"Campus Alberta Innovates Program","award":["#RCP-12-002C"],"award-info":[{"award-number":["#RCP-12-002C"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are emerging rapidly and offer surfaces that are optimized for recognition of host cell membranes while also evading antibodies arising from vaccinations and previous infections. Host cell infection is a multi-step process in which spike heads engage lipid bilayers and one or more angiotensin-converting enzyme 2 (ACE-2) receptors. Here, the membrane binding surfaces of Omicron subvariants are compared using cryo-electron microscopy (cEM) structures of spike trimers from BA.2, BA.2.12.1, BA.2.13, BA.2.75, BA.3, BA.4, and BA.5 viruses. Despite significant differences around mutated sites, they all maintain strong membrane binding propensities that first appeared in BA.1. Both their closed and open states retain elevated membrane docking capacities, although the presence of more closed than open states diminishes opportunities to bind receptors while enhancing membrane engagement. The electrostatic dipoles are generally conserved. However, the BA.2.75 spike dipole is compromised, and its ACE-2 affinity is increased, and BA.3 exhibits the opposite pattern. We propose that balancing the functional imperatives of a stable, readily cleavable spike that engages both lipid bilayers and receptors while avoiding host defenses underlies betacoronavirus evolution. This provides predictive criteria for rationalizing future pandemic waves and COVID-19 transmissibility while illuminating critical sites and strategies for simultaneously combating multiple variants.<\/jats:p>","DOI":"10.3390\/v15020447","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T04:08:07Z","timestamp":1675656487000},"page":"447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["SARS-CoV-2 Omicron Subvariants Balance Host Cell Membrane, Receptor, and Antibody Docking via an Overlapping Target Site"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3114-6585","authenticated-orcid":false,"given":"Michael","family":"Overduin","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7649-0470","authenticated-orcid":false,"given":"Rakesh K.","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7681-6861","authenticated-orcid":false,"given":"Troy A.","family":"Kervin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.coviro.2021.08.010","article-title":"Structure of SARS-CoV-2 spike protein","volume":"50","author":"Zhang","year":"2021","journal-title":"Curr. Opin. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s41586-022-04479-6","article-title":"SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo","volume":"603","author":"Hui","year":"2022","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1097\/PAS.0000000000001650","article-title":"Postmortem Findings Associated With SARS-CoV-2: Systematic Review and Meta-analysis","volume":"45","author":"Satturwar","year":"2021","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1016\/S1473-3099(22)00591-6","article-title":"Lung cell entry, cell-cell fusion capacity, and neutralisation sensitivity of omicron sublineage BA.2.75","volume":"22","author":"Arora","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/s41586-022-05053-w","article-title":"Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4 and BA.5","volume":"608","author":"Wang","year":"2022","journal-title":"Nature"},{"key":"ref_7","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_8","doi-asserted-by":"crossref","unstructured":"Cao, Y., Jian, F., Wang, J., Yu, Y., Song, W., Yisimayi, A., Wang, J., An, R., Zhang, N., and Wang, Y. (2022). Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution. BioRviv, 1\u20133. (In Press).","DOI":"10.1101\/2022.09.15.507787"},{"key":"ref_9","doi-asserted-by":"crossref","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":"2021","journal-title":"Bioinformatics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104722","DOI":"10.1016\/j.isci.2022.104722","article-title":"Progressive membrane-binding mechanism of SARS-CoV-2 variant spike proteins","volume":"25","author":"Overduin","year":"2022","journal-title":"iScience"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.crstbi.2022.05.001","article-title":"Multifaceted membrane binding head of the SARS-CoV-2 spike protein","volume":"4","author":"Tran","year":"2022","journal-title":"Curr. Res. Struct. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"D282","DOI":"10.1093\/nar\/gkaa731","article-title":"CoV3D: A database of high resolution coronavirus protein structures","volume":"49","author":"Gowthaman","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_13","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_14","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_15","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_16","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_17","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_18","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_19","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_20","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_21","unstructured":"Ni, D., Lau, K., Turelli, P., Raclot, C., Beckert, B., Nazarov, S., Pojer, F., Myasnikov, A., Stahlberg, H., and Trono, D. (2022). Structural analysis of the Spike of the Omicron SARS-COV-2 variant by cryo-EM and implications for immune evasion. bioRxiv."},{"key":"ref_22","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_23","doi-asserted-by":"crossref","unstructured":"Wang, L., Zhou, T., Zhang, Y., Yang, E.S., Schramm, C.A., Shi, W., Pegu, A., Oloninyi, O.K., Ransier, A., and Darko, S. (2021). Antibodies with potent and broad neutralizing activity against antigenically diverse and highly transmissible SARS-CoV-2 variants. bioRxiv.","DOI":"10.1101\/2021.02.25.432969"},{"key":"ref_24","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_25","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_26","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_27","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/j.chom.2022.10.003","article-title":"Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant","volume":"30","author":"Saito","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref_28","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_29","doi-asserted-by":"crossref","first-page":"5449","DOI":"10.1093\/bioinformatics\/btac680","article-title":"DREAMM: A web-based server for drugging protein-membrane interfaces as a novel workflow for targeted drug design","volume":"38","author":"Chatzigoulas","year":"2022","journal-title":"Bioinformatics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"bbab518","DOI":"10.1093\/bib\/bbab518","article-title":"Predicting protein-membrane interfaces of peripheral membrane proteins using ensemble machine learning","volume":"23","author":"Chatzigoulas","year":"2022","journal-title":"Brief. Bioinform."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.str.2012.03.016","article-title":"Knowledge-based potential for positioning membrane-associated structures and assessing residue-specific energetic contributions","volume":"20","author":"Schramm","year":"2012","journal-title":"Structure"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"D370","DOI":"10.1093\/nar\/gkr703","article-title":"OPM database and PPM web server: Resources for positioning of proteins in membranes","volume":"40","author":"Lomize","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/pro.4219","article-title":"Spatial arrangement of proteins in planar and curved membranes by PPM 3.0","volume":"31","author":"Lomize","year":"2022","journal-title":"Protein. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1139\/bcb-2014-0074","article-title":"Discovery of novel membrane binding structures and functions","volume":"92","author":"Kufareva","year":"2014","journal-title":"Biochem. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.devcel.2013.04.003","article-title":"Viral infection controlled by a calcium-dependent lipid-binding module in ALIX","volume":"25","author":"Bissig","year":"2013","journal-title":"Dev. Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e62614","DOI":"10.7554\/eLife.62614","article-title":"Structure of dual-BON domain protein DolP identifies phospholipid binding as a new mechanism for protein localization","volume":"9","author":"Bryant","year":"2020","journal-title":"Elife"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1080\/14789450.2021.1962302","article-title":"The phosphoinositide code is read by a plethora of protein domains","volume":"18","author":"Overduin","year":"2021","journal-title":"Expert. Rev. Proteomics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"646","DOI":"10.3390\/membranes5040646","article-title":"Membrane and Protein Interactions of the Pleckstrin Homology Domain Superfamily","volume":"5","author":"Lenoir","year":"2015","journal-title":"Membranes"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"D480","DOI":"10.1093\/nar\/gkaa1100","article-title":"UniProt: The universal protein knowledgebase in 2021","volume":"49","author":"Consortium","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1016\/j.cell.2022.06.005","article-title":"Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum","volume":"185","author":"Tuekprakhon","year":"2022","journal-title":"Cell"},{"key":"ref_41","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_42","doi-asserted-by":"crossref","unstructured":"Raush, E., Totrov, M., Marsden, B.D., and Abagyan, R. (2009). A new method for publishing three-dimensional content. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007394"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"W512","DOI":"10.1093\/nar\/gkm307","article-title":"A server and database for dipole moments of proteins","volume":"35","author":"Felder","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"eabo3153","DOI":"10.1126\/sciadv.abo3153","article-title":"Intermediates in SARS-CoV-2 spike-mediated cell entry","volume":"8","author":"Marcink","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_45","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_46","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/s41422-021-00490-0","article-title":"Structural basis for the different states of the spike protein of SARS-CoV-2 in complex with ACE2","volume":"31","author":"Yan","year":"2021","journal-title":"Cell Res."},{"key":"ref_47","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_48","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_49","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s13073-021-00985-w","article-title":"Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants","volume":"13","author":"Yi","year":"2021","journal-title":"Genome Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"111903","DOI":"10.1016\/j.celrep.2022.111903","article-title":"A delicate balance between antibody evasion and ACE2 affinity for Omicron BA.2.75","volume":"42","author":"Huo","year":"2022","journal-title":"Cell Rep."},{"key":"ref_51","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_52","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1021\/acs.jcim.1c01240","article-title":"Supramolecular Organization of SARS-CoV and SARS-CoV-2 Virions Revealed by Coarse-Grained Models of Intact Virus Envelopes","volume":"62","author":"Wang","year":"2021","journal-title":"J. Chem. Inf. Model"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s00795-021-00309-2","article-title":"Three-dimensional reconstruction by electron tomography for the application to ultrastructural analysis of SARS-CoV-2 particles","volume":"55","author":"Wu","year":"2022","journal-title":"Med. Mol. Morphol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1038\/s41598-022-07867-0","article-title":"An intra-cytoplasmic route for SARS-CoV-2 transmission unveiled by Helium-ion microscopy","volume":"12","author":"Merolli","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"55649","DOI":"10.1021\/acsami.0c17044","article-title":"Non-Receptor-Mediated Lipid Membrane Permeabilization by the SARS-CoV-2 Spike Protein S1 Subunit","volume":"12","author":"Asandei","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"14867","DOI":"10.1038\/s41598-021-93996-x","article-title":"Lipid bilayer degradation induced by SARS-CoV-2 spike protein as revealed by neutron reflectometry","volume":"11","author":"Luchini","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7098","DOI":"10.1002\/anie.202015639","article-title":"Molecular Simulations suggest Vitamins, Retinoids and Steroids as Ligands of the Free Fatty Acid Pocket of the SARS-CoV-2 Spike Protein*","volume":"60","author":"Shoemark","year":"2021","journal-title":"Angew Chem. Int. Ed. Engl."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/s42255-020-00324-0","article-title":"HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry","volume":"2","author":"Wei","year":"2020","journal-title":"Nat. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"109292","DOI":"10.1016\/j.celrep.2021.109292","article-title":"Recurrent emergence of SARS-CoV-2 spike deletion H69\/V70 and its role in the Alpha variant B.1.1.7","volume":"35","author":"Meng","year":"2021","journal-title":"Cell Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e65962","DOI":"10.7554\/eLife.65962","article-title":"SARS-CoV-2 requires cholesterol for viral entry and pathological syncytia formation","volume":"10","author":"Sanders","year":"2021","journal-title":"Elife"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.bbrc.2020.10.015","article-title":"Leveraging coronavirus binding to gangliosides for innovative vaccine and therapeutic strategies against COVID-19","volume":"538","author":"Fantini","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jinf.2021.06.001","article-title":"Structural dynamics of SARS-CoV-2 variants: A health monitoring strategy for anticipating Covid-19 outbreaks","volume":"83","author":"Fantini","year":"2021","journal-title":"J. Infect."},{"key":"ref_63","first-page":"1196503","article-title":"Localization-Based Super-Resolution Microscopy Reveals Relationship between SARS-CoV2 Spike and Phosphatidylinositol (4,5)-bisphosphate","volume":"11965","author":"Raut","year":"2022","journal-title":"Proc. SPIE Int. Soc. Opt. Eng."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Carrique, L., Duyvesteyn, H.M., Malinauskas, T., Zhao, Y., Ren, J., Zhou, D., Walter, T.S., Radecke, J., Huo, J., and Ruza, R.R. (2020). The SARS-CoV-2 Spike Harbours a Lipid Binding Pocket Which Modulates Stability of the Prefusion Trimer. bioRxiv.","DOI":"10.1101\/2020.08.13.249177"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/s41589-021-00924-1","article-title":"Sialic acid-containing glycolipids mediate binding and viral entry of SARS-CoV-2","volume":"18","author":"Nguyen","year":"2021","journal-title":"Nat. Chem. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.cell.2020.09.033","article-title":"SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2","volume":"183","author":"Clausen","year":"2020","journal-title":"Cell"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Shi, D., Bu, C., He, P., Song, Y., Dordick, J.S., Linhardt, R.J., Chi, L., and Zhang, F. (2022). Structural Characteristics of Heparin Binding to SARS-CoV-2 Spike Protein RBD of Omicron Sub-Lineages BA.2.12.1, BA.4 and BA.5. Viruses, 14.","DOI":"10.3390\/v14122696"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"8890","DOI":"10.1073\/pnas.1910670117","article-title":"Cryo-EM structure of eastern equine encephalitis virus in complex with heparan sulfate analogues","volume":"117","author":"Chen","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4629","DOI":"10.1038\/s41467-021-24887-y","article-title":"Correlative multi-scale cryo-imaging unveils SARS-CoV-2 assembly and egress","volume":"12","author":"Howe","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5885","DOI":"10.1038\/s41467-020-19619-7","article-title":"SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography","volume":"11","author":"Klein","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/boc.202000146","article-title":"Intracellular host cell membrane remodelling induced by SARS-CoV-2 infection in vitro","volume":"113","author":"Caldas","year":"2021","journal-title":"Biol. Cell."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3565","DOI":"10.1007\/s00018-020-03745-y","article-title":"Ultrastructural modifications induced by SARS-CoV-2 in Vero cells: A kinetic analysis of viral factory formation, viral particle morphogenesis and virion release","volume":"78","author":"Eymieux","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1038\/s41467-022-29255-y","article-title":"Ultrastructural insight into SARS-CoV-2 entry and budding in human airway epithelium","volume":"13","author":"Pinto","year":"2022","journal-title":"Nat. Commun."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/2\/447\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:25:14Z","timestamp":1760120714000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/2\/447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,6]]},"references-count":73,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["v15020447"],"URL":"https:\/\/doi.org\/10.3390\/v15020447","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,6]]}}}