{"doi":"10.1126/science.adn5658","title":"Structure and inhibition of SARS-CoV-2 spike refolding in membranes","abstract":"The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds the receptor angiotensin converting enzyme 2 (ACE2) and drives virus-host membrane fusion through refolding of its S2 domain. Whereas the S1 domain contains high sequence variability, the S2 domain is conserved and is a promising pan-betacoronavirus vaccine target. We applied cryo-electron tomography to capture intermediates of S2 refolding and understand inhibition by antibodies to the S2 stem-helix. Subtomogram averaging revealed ACE2 dimers cross-linking spikes before transitioning into S2 intermediates, which were captured at various stages of refolding. Pan-betacoronavirus neutralizing antibodies targeting the S2 stem-helix bound to and inhibited refolding of spike prehairpin intermediates. Combined with molecular dynamics simulations, these structures elucidate the process of SARS-CoV-2 entry and reveal how pan-betacoronavirus S2-targeting antibodies neutralize infectivity by arresting prehairpin intermediates.","journal":"Science","year":2024,"id":418359,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":52,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9621,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":994351,"name":"Zhuan Qin","orcid":"0000-0001-9112-7645","position":1,"is_corresponding":false},{"id":29882,"name":"Esteban Dodero-Rojas","orcid":"0000-0001-9054-9555","position":2,"is_corresponding":false},{"id":241572,"name":"Shilei Ding","orcid":"0000-0003-1895-5131","position":3,"is_corresponding":false},{"id":241563,"name":"Jérémie Prévost","orcid":"0000-0002-5260-5154","position":4,"is_corresponding":false},{"id":467518,"name":"Yaozong Chen","orcid":"0000-0001-5380-2339","position":5,"is_corresponding":false},{"id":1030556,"name":"Yanping Hu","orcid":"0009-0006-8820-7437","position":6,"is_corresponding":false},{"id":335148,"name":"Marzena Pazgier","orcid":"0000-0003-0594-5057","position":7,"is_corresponding":false},{"id":246109,"name":"Shenping Wu","orcid":"0000-0002-4295-4318","position":8,"is_corresponding":false},{"id":105317,"name":"Xuping Xie","orcid":"0000-0003-0918-016X","position":9,"is_corresponding":false},{"id":241588,"name":"Andrés Finzi","orcid":"0000-0002-4992-5288","position":10,"is_corresponding":false},{"id":29885,"name":"José N. Onuchic","orcid":"0000-0002-9448-0388","position":11,"is_corresponding":false},{"id":459765,"name":"Paul C. Whitford","orcid":"0000-0001-7104-2265","position":12,"is_corresponding":false},{"id":241931,"name":"Walther Mothes","orcid":"0000-0002-3367-7240","position":13,"is_corresponding":false},{"id":241925,"name":"Wenwei Li","orcid":"0000-0003-3008-6901","position":14,"is_corresponding":false},{"id":381201,"name":"Michael W. Grunst","orcid":"0000-0002-8575-8026","position":0,"is_corresponding":true}],"reference_count":102,"raw_metadata":null,"created_at":"2026-07-19T01:57:02.483590Z","pmid":"39146425","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}