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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,5,2]]},"abstract":"<jats:p>Among the current five Variants of Concern, infections caused by SARS-CoV-2 B.1.617.2 (Delta) variant are often associated with the greatest severity. Despite recent advances on the molecular basis of elevated pathogenicity using recombinant proteins, the architecture of intact Delta virions remains veiled. Moreover, pieces of molecular evidence for the detailed mechanism of S-mediated membrane fusion are missing. Here, we showed the pleomorphic nature of Delta virions from electron beam inactivated samples and reported the in\u00a0situ structure and distribution of S on the authentic Delta variant. We also captured the virus\u2013virus fusion events, which provided pieces of structural evidence for Delta\u2019s attenuated dependency on cellular factors for fusion activation, and proposed a model of S-mediated membrane fusion. Besides, site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S than that of the WT S. Together, these results disclose distinctive factors of Delta being the most virulent SARS-CoV-2 variant.<\/jats:p>","DOI":"10.1073\/pnas.2213332120","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T15:12:52Z","timestamp":1682349172000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":36,"title":["In situ architecture and membrane fusion of SARS-CoV-2 Delta variant"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2206-9549","authenticated-orcid":false,"given":"Yutong","family":"Song","sequence":"first","affiliation":[{"name":"State Key Laboratory of Membrane Biology &amp; Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing 100084, China"},{"name":"Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6742-7074","authenticated-orcid":false,"given":"Hangping","family":"Yao","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China"},{"name":"National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanping","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China"},{"name":"National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialu","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology &amp; 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C. Marcink Intermediates in SARS-CoV-2 spike\u2013mediated cell entry. Sci. Adv. 8 eabo3153 (2022). eabo3153","DOI":"10.1126\/sciadv.abo3153"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19619-7"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.10.039"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.100849"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2016.06.007"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2005.07.007"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4193"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2015.08.008"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2017.07.007"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1006\/jsbi.1996.0013"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33957-8"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2012.05.001"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0582-9"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2011.12.017"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0580-y"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0575-8"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2012.09.006"},{"key":"e_1_3_4_49_2","doi-asserted-by":"crossref","unstructured":"J. Xu Cryo-EM structure of SARS-CoV-2 Delta variant prefusion S in closed conformation. EMDB. https:\/\/www.ebi.ac.uk\/emdb\/EMD-33205. Deposited 13 April 2022.","DOI":"10.2210\/pdb7y6d\/pdb"},{"key":"e_1_3_4_50_2","unstructured":"Y. Song Subtomogram average of SARS-CoV-2 Delta variant prefusion S in closed conformation. EMDB. https:\/\/www.ebi.ac.uk\/emdb\/EMD-33206. Deposited 13 April 2022."},{"key":"e_1_3_4_51_2","unstructured":"Y. Song Subtomogram average of SARS-CoV-2 Delta variant prefusion S in one RBD up conformation. EMDB. https:\/\/www.ebi.ac.uk\/emdb\/EMD-33207. Deposited 13 April 2022."},{"key":"e_1_3_4_52_2","unstructured":"Y. Song Subtomogram average of SARS-CoV-2 Delta variant postfusion S. EMDB. https:\/\/www.ebi.ac.uk\/emdb\/EMD-33208. Deposited 13 April 2022."},{"key":"e_1_3_4_53_2","unstructured":"Y. Song Tilt series of E-beam inactivated SARS-CoV-2 Delta virions. EMPIAR. https:\/\/www.ebi.ac.uk\/empiar\/EMPIAR-11478\/. 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Deposited 21 April 2022."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2213332120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T09:34:13Z","timestamp":1695288853000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2213332120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,24]]},"references-count":57,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2023,5,2]]}},"alternative-id":["10.1073\/pnas.2213332120"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2213332120","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.05.13.491759","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,24]]},"assertion":[{"value":"2022-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2213332120"}}