{"doi":"10.1016/j.celrep.2021.109760","title":"Broad cross-reactivity across sarbecoviruses exhibited by a subset of COVID-19 donor-derived neutralizing antibodies","abstract":"Many anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) neutralizing antibodies target the angiotensin-converting enzyme 2 (ACE2) binding site on viral spike receptor-binding domains (RBDs). Potent antibodies recognize exposed variable epitopes, often rendering them ineffective against other sarbecoviruses and SARS-CoV-2 variants. Class 4 anti-RBD antibodies against a less-exposed, but more-conserved, cryptic epitope could recognize newly emergent zoonotic sarbecoviruses and variants, but they usually show only weak neutralization potencies. Here, we characterize two class 4 anti-RBD antibodies derived from coronavirus disease 2019 (COVID-19) donors that exhibit breadth and potent neutralization of zoonotic coronaviruses and SARS-CoV-2 variants. C118-RBD and C022-RBD structures reveal orientations that extend from the cryptic epitope to occlude ACE2 binding and CDRH3-RBD main-chain H-bond interactions that extend an RBD β sheet, thus reducing sensitivity to RBD side-chain changes. A C118-spike trimer structure reveals rotated RBDs that allow access to the cryptic epitope and the potential for intra-spike crosslinking to increase avidity. These studies facilitate vaccine design and illustrate potential advantages of class 4 RBD-binding antibody therapeutics.","journal":"Cell Reports","year":2021,"id":148346,"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":129,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9529,"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":16982,"name":"Alexander A. Cohen","orcid":"0000-0002-2818-656X","position":1,"is_corresponding":false},{"id":16983,"name":"Priyanthi N.P. Gnanapragasam","orcid":null,"position":2,"is_corresponding":false},{"id":16973,"name":"Frauke Muecksch","orcid":"0000-0002-0132-5101","position":3,"is_corresponding":false},{"id":105101,"name":"Yu E. Lee","orcid":"0000-0001-5989-326X","position":4,"is_corresponding":false},{"id":16998,"name":"Kathryn E. Huey‐Tubman","orcid":"0000-0002-4683-8138","position":5,"is_corresponding":false},{"id":104730,"name":"Fabian Schmidt","orcid":"0000-0001-7731-6685","position":6,"is_corresponding":false},{"id":104738,"name":"Théodora Hatziioannou","orcid":"0000-0002-7889-0766","position":7,"is_corresponding":false},{"id":16992,"name":"Paul D. Bieniasz","orcid":"0000-0002-2368-3719","position":8,"is_corresponding":false},{"id":104187,"name":"Michel C. Nussenzweig","orcid":"0000-0003-0592-8564","position":9,"is_corresponding":false},{"id":104736,"name":"Anthony P. West","orcid":"0000-0003-4213-5184","position":10,"is_corresponding":false},{"id":16970,"name":"Jennifer R. Keeffe","orcid":"0000-0002-5317-6398","position":11,"is_corresponding":false},{"id":17000,"name":"Pamela J. Björkman","orcid":"0000-0002-2277-3990","position":12,"is_corresponding":false},{"id":16968,"name":"Christopher O. Barnes","orcid":"0000-0003-2754-5951","position":13,"is_corresponding":false},{"id":105094,"name":"Claudia A. Jette","orcid":"0000-0002-5085-8027","position":0,"is_corresponding":true}],"reference_count":122,"raw_metadata":null,"created_at":"2026-07-18T23:42:41.063423Z","pmid":"34534459","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":[]}