{"doi":"10.1101/2022.01.12.476120","title":"An antibody targeting the N-terminal domain of SARS-CoV-2 disrupts the spike trimer","abstract":"SUMMARY The protective human antibody response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus focuses on the spike (S) protein which decorates the virion surface and mediates cell binding and entry. Most SARS-CoV-2 protective antibodies target the receptor- binding domain or a single dominant epitope (‘supersite’) on the N terminal domain (NTD). Here, using the single B cell technology LIBRA-seq, we isolated a large panel of NTD-reactive and SARS-CoV-2 neutralizing antibodies from an individual who had recovered from COVID-19. We found that neutralizing antibodies to the NTD supersite commonly are encoded by the IGHV1-24 gene, forming a genetic cluster that represents a public B cell clonotype. However, we also discovered a rare human antibody, COV2-3434, that recognizes a site of vulnerability on the SARS-CoV-2 S protein in the trimer interface and possesses a distinct class of functional activity. COV2-3434 disrupted the integrity of S protein trimers, inhibited cell-to-cell spread of virus in culture, and conferred protection in human ACE2 transgenic mice against SARS-CoV-2 challenge. This study provides insight about antibody targeting of the S protein trimer interface region, suggesting this region may be a site of virus vulnerability.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":299739,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.963,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":559636,"name":"Andrea R. Shiakolas","orcid":"0000-0001-9391-5434","position":1,"is_corresponding":false},{"id":550303,"name":"Laura A. VanBlargan","orcid":"0000-0002-8922-8946","position":2,"is_corresponding":false},{"id":106499,"name":"Elad Binshtein","orcid":"0000-0003-2745-104X","position":3,"is_corresponding":false},{"id":106500,"name":"Rita E. Chen","orcid":"0000-0002-5100-7750","position":4,"is_corresponding":false},{"id":106498,"name":"James Brett Case","orcid":"0000-0001-7331-5511","position":5,"is_corresponding":false},{"id":559637,"name":"Kevin J. Kramer","orcid":"0000-0001-8451-9018","position":6,"is_corresponding":false},{"id":460553,"name":"Erica Armstrong","orcid":null,"position":7,"is_corresponding":false},{"id":106511,"name":"Luke Myers","orcid":"0000-0003-1132-2550","position":8,"is_corresponding":false},{"id":106503,"name":"Andrew Trivette","orcid":null,"position":9,"is_corresponding":false},{"id":619703,"name":"Christopher Gainza","orcid":null,"position":10,"is_corresponding":false},{"id":106504,"name":"Rachel S. Nargi","orcid":null,"position":11,"is_corresponding":false},{"id":651953,"name":"Christopher N. Selverian","orcid":"0000-0002-1047-4336","position":12,"is_corresponding":false},{"id":283937,"name":"Edgar Davidson","orcid":"0000-0002-3333-2314","position":13,"is_corresponding":false},{"id":283938,"name":"Benjamin J. Doranz","orcid":"0000-0002-8245-3083","position":14,"is_corresponding":false},{"id":884119,"name":"Summer M. Diaz","orcid":null,"position":15,"is_corresponding":false},{"id":883551,"name":"Laura S. Handal","orcid":"0000-0001-8658-4411","position":16,"is_corresponding":false},{"id":106530,"name":"Robert H. Carnahan","orcid":"0000-0001-5230-1532","position":17,"is_corresponding":false},{"id":106529,"name":"Michael Diamond","orcid":"0000-0002-8791-3165","position":18,"is_corresponding":false},{"id":290894,"name":"Ivelin S. Georgiev","orcid":"0000-0002-6312-7696","position":19,"is_corresponding":false},{"id":106531,"name":"James E. Crowe","orcid":"0000-0002-0049-1079","position":20,"is_corresponding":false},{"id":106506,"name":"Naveenchandra Suryadevara","orcid":"0000-0003-2571-1290","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:49.412501Z","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":[]}