{"doi":"10.1172/jci178880","title":"Structural characterization of human monoclonal antibodies targeting uncommon antigenic sites on spike glycoprotein of SARS-CoV","abstract":"The function of the spike protein N terminal domain (NTD) in coronavirus (CoV) infections is poorly understood. However, some rare antibodies that target the SARS-CoV-2 NTD potently neutralize the virus. This finding suggests the NTD may contribute, in part, to protective immunity. Pansarbecovirus antibodies are desirable for broad protection, but the NTD region of SARS-CoV and SARS-CoV-2 exhibit a high level of sequence divergence; therefore, cross-reactive NTD-specific antibodies are unexpected, and there is no structure of a SARS-CoV NTD-specific antibody in complex with NTD. Here, we report a monoclonal antibody COV1-65, encoded by the IGHV1-69 gene, that recognizes the NTD of SARS-CoV S protein. A prophylaxis study showed the mAb COV1-65 prevented disease when administered before SARS-CoV challenge of BALB/c mice, an effect that requires intact fragment crystallizable region (Fc) effector functions for optimal protection in vivo. The footprint on the S protein of COV1-65 is near to functional components of the S2 fusion machinery, and the selection of COV1-65 escape mutant viruses identified critical residues Y886H and Q974H, which likely affect the epitope through allosteric effects. Structural features of the mAb COV1-65-SARS-CoV antigen interaction suggest critical antigenic determinants that should be considered in the rational design of sarbecovirus vaccine candidates.","journal":"Journal of Clinical Investigation","year":2024,"id":460473,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"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":296074,"name":"Nurgun Kose","orcid":"0000-0001-7425-292X","position":1,"is_corresponding":false},{"id":230740,"name":"Sandhya Bangaru","orcid":"0000-0001-7994-4693","position":2,"is_corresponding":false},{"id":106499,"name":"Elad Binshtein","orcid":"0000-0003-2745-104X","position":3,"is_corresponding":false},{"id":355496,"name":"Jennifer E. Munt","orcid":"0000-0002-1169-025X","position":4,"is_corresponding":false},{"id":540773,"name":"David R. Martinez","orcid":"0000-0002-1689-5529","position":5,"is_corresponding":false},{"id":105112,"name":"Alexandra Schäfer","orcid":null,"position":6,"is_corresponding":false},{"id":106511,"name":"Luke Myers","orcid":"0000-0003-1132-2550","position":7,"is_corresponding":false},{"id":254645,"name":"Trevor Scobey","orcid":"0000-0001-8313-5434","position":8,"is_corresponding":false},{"id":106530,"name":"Robert H. Carnahan","orcid":"0000-0001-5230-1532","position":9,"is_corresponding":false},{"id":230082,"name":"Andrew B. Ward","orcid":"0000-0001-7153-3769","position":10,"is_corresponding":false},{"id":5952,"name":"Ralph S. Baric","orcid":"0000-0001-6827-8701","position":11,"is_corresponding":false},{"id":106531,"name":"James E. Crowe","orcid":"0000-0002-0049-1079","position":12,"is_corresponding":false},{"id":106506,"name":"Naveenchandra Suryadevara","orcid":"0000-0003-2571-1290","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T02:04:07.925246Z","pmid":"39589795","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":[]}