{"doi":"10.1016/j.cell.2024.09.026","title":"A potent pan-sarbecovirus neutralizing antibody resilient to epitope diversification","abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing coronavirus mAbs that are sufficiently potent for clinical development and retain activity despite viral evolution remain elusive. We identified a human mAb, designated VIR-7229, which targets the viral receptor-binding motif (RBM) with unprecedented cross-reactivity to all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently neutralizing SARS-CoV-2 variants since 2019, including the recent EG.5, BA.2.86, and JN.1. VIR-7229 tolerates extraordinary epitope variability, partly attributed to its high binding affinity, receptor molecular mimicry, and interactions with RBM backbone atoms. Consequently, VIR-7229 features a high barrier for selection of escape mutants, which are rare and associated with reduced viral fitness, underscoring its potential to be resilient to future viral evolution. VIR-7229 is a strong candidate to become a next-generation medicine.","journal":"Cell","year":2024,"id":417465,"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":69,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"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":97048,"name":"M. Alejandra Tortorici","orcid":"0000-0002-2260-2577","position":1,"is_corresponding":false},{"id":217928,"name":"Anna De Marco","orcid":"0000-0001-9641-4838","position":2,"is_corresponding":false},{"id":217922,"name":"Dora Pinto","orcid":"0000-0001-5737-8467","position":3,"is_corresponding":false},{"id":1203133,"name":"William Foreman","orcid":"0000-0003-0784-214X","position":4,"is_corresponding":false},{"id":1028033,"name":"Ashley L. Taylor","orcid":"0000-0001-9975-7596","position":5,"is_corresponding":false},{"id":97052,"name":"Young‐Jun Park","orcid":"0000-0003-2901-6949","position":6,"is_corresponding":false},{"id":372343,"name":"Dana Bohan","orcid":"0000-0002-9239-3053","position":7,"is_corresponding":false},{"id":873007,"name":"Tyson A. Rietz","orcid":"0000-0003-4670-5279","position":8,"is_corresponding":false},{"id":262619,"name":"John M. Errico","orcid":"0000-0002-4452-8152","position":9,"is_corresponding":false},{"id":73317,"name":"Kevin Hauser","orcid":"0000-0002-4579-4794","position":10,"is_corresponding":false},{"id":225080,"name":"Ha V. Dang","orcid":"0000-0003-1173-9241","position":11,"is_corresponding":false},{"id":739617,"name":"Justin W. Chartron","orcid":"0000-0003-1734-3424","position":12,"is_corresponding":false},{"id":842919,"name":"Martina Giurdanella","orcid":null,"position":13,"is_corresponding":false},{"id":1203731,"name":"Giuseppe Cusumano","orcid":null,"position":14,"is_corresponding":false},{"id":614553,"name":"Christian Saliba","orcid":"0000-0003-0100-6976","position":15,"is_corresponding":false},{"id":217927,"name":"Fabrizia Zatta","orcid":"0000-0003-4945-8058","position":16,"is_corresponding":false},{"id":614555,"name":"Kaitlin R. Sprouse","orcid":"0000-0003-0007-2226","position":17,"is_corresponding":false},{"id":294604,"name":"Amin Addetia","orcid":"0000-0001-6703-3841","position":18,"is_corresponding":false},{"id":614554,"name":"Samantha K. Zepeda","orcid":"0000-0003-0005-9793","position":19,"is_corresponding":false},{"id":732002,"name":"Jack Brown","orcid":null,"position":20,"is_corresponding":false},{"id":1034562,"name":"Jimin Lee","orcid":"0000-0001-5849-7732","position":21,"is_corresponding":false},{"id":615526,"name":"Exequiel Dellota","orcid":"0000-0002-2006-3880","position":22,"is_corresponding":false},{"id":841613,"name":"Anushka Rajesh","orcid":"0000-0002-7729-0865","position":23,"is_corresponding":false},{"id":103696,"name":"Julia Noack","orcid":"0000-0002-9113-8181","position":24,"is_corresponding":false},{"id":381445,"name":"Qiqing Tao","orcid":"0000-0001-7360-409X","position":25,"is_corresponding":false},{"id":1203732,"name":"Yvonne DaCosta","orcid":null,"position":26,"is_corresponding":false},{"id":555503,"name":"Brian V. Tsu","orcid":"0000-0003-0268-8323","position":27,"is_corresponding":false},{"id":1103931,"name":"Rima Acosta","orcid":"0000-0002-0255-9487","position":28,"is_corresponding":false},{"id":883836,"name":"Sambhavi Subramanian","orcid":null,"position":29,"is_corresponding":false},{"id":841616,"name":"Guilherme Dias de Melo","orcid":"0000-0003-0747-7760","position":30,"is_corresponding":false},{"id":841617,"name":"Lauriane Kergoat","orcid":"0000-0002-5609-4398","position":31,"is_corresponding":false},{"id":615330,"name":"Ivy Zhang","orcid":"0000-0003-0628-6276","position":32,"is_corresponding":false},{"id":106714,"name":"Zhuoming Liu","orcid":"0000-0001-8198-0976","position":33,"is_corresponding":false},{"id":217930,"name":"Barbara Guarino","orcid":"0000-0003-3759-3252","position":34,"is_corresponding":false},{"id":80059,"name":"Michael A. Schmid","orcid":"0000-0002-1137-9322","position":35,"is_corresponding":false},{"id":593344,"name":"Gretja Schnell","orcid":"0000-0002-2085-7314","position":36,"is_corresponding":false},{"id":1203134,"name":"Jessica L. Miller","orcid":"0000-0001-6080-6143","position":37,"is_corresponding":false},{"id":225079,"name":"Florian A. Lempp","orcid":"0000-0001-6103-8078","position":38,"is_corresponding":false},{"id":218040,"name":"Nadine Czudnochowski","orcid":"0000-0002-0771-0721","position":39,"is_corresponding":false},{"id":217932,"name":"Elisabetta Cameroni","orcid":"0000-0002-9102-8943","position":40,"is_corresponding":false},{"id":103752,"name":"Sean P. J. Whelan","orcid":"0000-0003-1564-8590","position":41,"is_corresponding":false},{"id":841618,"name":"Hervé Bourhy","orcid":"0000-0002-2608-5589","position":42,"is_corresponding":false},{"id":581272,"name":"Lisa A. Purcell","orcid":"0000-0002-9565-2030","position":43,"is_corresponding":false},{"id":80081,"name":"Fabio Benigni","orcid":"0000-0002-1974-5606","position":44,"is_corresponding":false},{"id":457647,"name":"Julia di Iulio","orcid":"0000-0001-9343-127X","position":45,"is_corresponding":false},{"id":218059,"name":"Matteo Samuele Pizzuto","orcid":null,"position":46,"is_corresponding":false},{"id":217935,"name":"Antonio Lanzavecchia","orcid":"0000-0002-3041-7240","position":47,"is_corresponding":false},{"id":29722,"name":"Amalio Telenti","orcid":"0000-0001-6290-7677","position":48,"is_corresponding":false},{"id":50306,"name":"Gyorgy Snell","orcid":null,"position":49,"is_corresponding":false},{"id":80082,"name":"Davide Corti","orcid":"0000-0002-5797-1364","position":50,"is_corresponding":false},{"id":97051,"name":"David Veesler","orcid":"0000-0002-6019-8675","position":51,"is_corresponding":false},{"id":106706,"name":"Tyler N. Starr","orcid":"0000-0001-6713-6904","position":52,"is_corresponding":false},{"id":218042,"name":"Laura E. Rosen","orcid":"0000-0002-8030-0219","position":0,"is_corresponding":true}],"reference_count":125,"raw_metadata":null,"created_at":"2026-07-19T01:56:50.743370Z","pmid":"39383863","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":[]}