{"doi":"10.1101/2021.01.31.428824","title":"Identification of a conserved neutralizing epitope present on spike proteins from all highly pathogenic coronaviruses","abstract":"ABSTRACT Three pathogenic human coronaviruses have emerged within the last 20 years, with SARS-CoV-2 causing a global pandemic. Although therapeutic antibodies targeting the SARS-CoV-2 spike currently focus on the poorly conserved receptor-binding domain, targeting essential neutralizing epitopes on the more conserved S2 domain may provide broader protection. We report an antibody binding an epitope conserved in the pre-fusion core of MERS-CoV, SARS-CoV and SARS-CoV-2 spike S2 domains. Antibody 3A3 binds a conformational epitope with ~2.5 nM affinity and neutralizes spike from SARS-CoV, SARS-CoV-2 and variants of concern in in vitro pseudovirus assays. Hydrogen-deuterium exchange mass spectrometry identified residues 980-1006 in the flexible hinge region at the S2 apex as the 3A3 epitope, suggesting 3A3 prevents the S2 conformational rearrangements required for conversion to the spike post-fusion state and virus-host cell fusion. This work defines a conserved vulnerable site on the SARS-CoV-2 S2 domain and guides the design of pan-protective spike immunogens.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":213097,"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":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9605,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105929,"name":"Annalee W. Nguyen","orcid":"0000-0003-1268-7164","position":1,"is_corresponding":false},{"id":87313,"name":"Ching‐Lin Hsieh","orcid":"0000-0002-3665-5717","position":2,"is_corresponding":false},{"id":804359,"name":"Rui Silva","orcid":"0000-0001-5470-778X","position":3,"is_corresponding":false},{"id":804360,"name":"Oladimeji S. Olaluwoye","orcid":"0000-0002-7888-0672","position":4,"is_corresponding":false},{"id":804953,"name":"Rebecca E Wilen","orcid":null,"position":5,"is_corresponding":false},{"id":768122,"name":"Tamer S. Kaoud","orcid":"0000-0003-1298-8725","position":6,"is_corresponding":false},{"id":804361,"name":"Laura R. Azouz","orcid":"0000-0002-9423-6000","position":7,"is_corresponding":false},{"id":804362,"name":"Ahlam N. Qerqez","orcid":"0000-0003-4694-5619","position":8,"is_corresponding":false},{"id":105921,"name":"Kevin Le","orcid":"0000-0001-5098-7737","position":9,"is_corresponding":false},{"id":804363,"name":"Amanda L. Bohanon","orcid":"0000-0002-3371-3416","position":10,"is_corresponding":false},{"id":105918,"name":"Andrea M. DiVenere","orcid":"0000-0001-9254-5347","position":11,"is_corresponding":false},{"id":105923,"name":"Yutong Liu","orcid":"0000-0003-0626-8094","position":12,"is_corresponding":false},{"id":105922,"name":"Alison G. Lee","orcid":"0000-0001-8305-3332","position":13,"is_corresponding":false},{"id":105931,"name":"Dzifa Amengor","orcid":"0000-0001-5705-3259","position":14,"is_corresponding":false},{"id":804364,"name":"Sophie R. Shoemaker","orcid":"0000-0002-5278-2361","position":15,"is_corresponding":false},{"id":804365,"name":"Shawn M. Costello","orcid":"0000-0003-3926-8074","position":16,"is_corresponding":false},{"id":478687,"name":"Susan Marqusee","orcid":"0000-0001-7648-2163","position":17,"is_corresponding":false},{"id":292931,"name":"Kevin N. Dalby","orcid":"0000-0001-9272-5129","position":18,"is_corresponding":false},{"id":470881,"name":"Sheena D’Arcy","orcid":"0000-0001-5055-988X","position":19,"is_corresponding":false},{"id":87312,"name":"Jason S. McLellan","orcid":"0000-0003-3991-542X","position":20,"is_corresponding":false},{"id":105934,"name":"Jennifer A. Maynard","orcid":"0000-0002-0363-8486","position":21,"is_corresponding":false},{"id":242701,"name":"Yimin Huang","orcid":"0000-0003-4348-5688","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-18T23:52:31.378994Z","pmid":null,"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":[]}