{"doi":"10.1101/2020.03.15.992883","title":"A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike Glycoprotein","abstract":"SARS-CoV-2 is a zoonotic virus that has caused a pandemic of severe respiratory disease-COVID-19-within several months of its initial identification. Comparable to the first SARS-CoV, this novel coronavirus's surface Spike (S) glycoprotein mediates cell entry via the human ACE-2 receptor, and, thus, is the principal target for the development of vaccines and immunotherapeutics. Molecular information on the SARS-CoV-2 S glycoprotein remains limited. Here we report the crystal structure of the SARS-CoV-2 S receptor-binding-domain (RBD) at a the highest resolution to date, of 1.95 Å. We identified a set of SARS-reactive monoclonal antibodies with cross-reactivity to SARS-CoV-2 RBD and other betacoronavirus S glycoproteins. One of these antibodies, CR3022, was previously shown to synergize with antibodies that target the ACE-2 binding site on the SARS-CoV RBD and reduce viral escape capacity. We determined the structure of CR3022, in complex with the SARS-CoV-2 RBD, and defined a broadly reactive epitope that is highly conserved across betacoronaviruses. This epitope is inaccessible in the \"closed\" prefusion S structure, but is accessible in \"open\" conformations. This first-ever resolution of a human antibody in complex with SARS-CoV-2 and the broad reactivity of this set of antibodies to a conserved betacoronavirus epitope will allow antigenic assessment of vaccine candidates, and provide a framework for accelerated vaccine, immunotherapeutic and diagnostic strategies against SARS-CoV-2 and related betacoronaviruses.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":118627,"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":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":293301,"name":"Rajeshwer S. Sankhala","orcid":null,"position":1,"is_corresponding":false},{"id":551664,"name":"Wei‐Hung Chen","orcid":"0000-0003-3724-9195","position":2,"is_corresponding":false},{"id":293305,"name":"Misook Choe","orcid":null,"position":3,"is_corresponding":false},{"id":290882,"name":"Hongjun Bai","orcid":"0000-0002-3501-3974","position":4,"is_corresponding":false},{"id":382445,"name":"Agnes Hajduczki","orcid":null,"position":5,"is_corresponding":false},{"id":551665,"name":"Lianying Yan","orcid":"0000-0003-1663-1205","position":6,"is_corresponding":false},{"id":551666,"name":"Spencer L. Sterling","orcid":"0000-0002-5924-4056","position":7,"is_corresponding":false},{"id":551667,"name":"Caroline E. Peterson","orcid":"0000-0002-6087-7301","position":8,"is_corresponding":false},{"id":552931,"name":"Ethan C. Green","orcid":null,"position":9,"is_corresponding":false},{"id":351085,"name":"Clayton Smith","orcid":"0000-0002-8509-6237","position":10,"is_corresponding":false},{"id":228429,"name":"Natalia de Val","orcid":"0000-0002-1506-2023","position":11,"is_corresponding":false},{"id":251094,"name":"Mihret F. Amare","orcid":"0000-0002-2696-6116","position":12,"is_corresponding":false},{"id":551668,"name":"Paul T. Scott","orcid":"0000-0002-2348-4541","position":13,"is_corresponding":false},{"id":533696,"name":"Eric D. Laing","orcid":"0000-0002-5574-2584","position":14,"is_corresponding":false},{"id":533697,"name":"Christopher C. Broder","orcid":"0000-0001-5382-0510","position":15,"is_corresponding":false},{"id":36876,"name":"Morgane Rolland","orcid":"0000-0003-3650-8490","position":16,"is_corresponding":false},{"id":40990,"name":"Nelson L. Michael","orcid":"0000-0001-5882-5548","position":17,"is_corresponding":false},{"id":251098,"name":"Kayvon Modjarrad","orcid":"0000-0002-6514-5572","position":18,"is_corresponding":false},{"id":290901,"name":"Michael Joyce","orcid":"0000-0002-6808-7232","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-18T23:14:03.409507Z","pmid":"32511298","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":[]}