{"doi":"10.1101/2021.09.14.460356","title":"Rapid Identification of Neutralizing Antibodies against SARS-CoV-2 Variants by mRNA Display","abstract":"The increasing prevalence of SARS-CoV-2 variants with the ability to escape existing humoral protection conferred by previous infection and/or immunization necessitates the discovery of broadly-reactive neutralizing antibodies (nAbs). Utilizing mRNA display, we identified a set of antibodies against SARS-CoV-2 spike (S) proteins and characterized the structures of nAbs that recognized epitopes in the S1 subunit of the S glycoprotein. These structural studies revealed distinct binding modes for several antibodies, including targeting of rare cryptic epitopes in the receptor-binding domain (RBD) of S that interacts with angiotensin- converting enzyme 2 (ACE2) to initiate infection, as well as the S1 subdomain 1. A potent ACE2-blocking nAb was further engineered to sustain binding to S RBD with the E484K and L452R substitutions found in multiple SARS-CoV-2 variants. We demonstrate that mRNA display is a promising approach for the rapid identification of nAbs that can be used in combination to combat emerging SARS-CoV-2 variants.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":226728,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"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":433766,"name":"C. Anders Olson","orcid":"0000-0002-5382-1393","position":1,"is_corresponding":false},{"id":16968,"name":"Christopher O. Barnes","orcid":"0000-0003-2754-5951","position":2,"is_corresponding":false},{"id":830570,"name":"Wendy Higashide","orcid":null,"position":3,"is_corresponding":false},{"id":830571,"name":"M Aguilar Gonzalez","orcid":null,"position":4,"is_corresponding":false},{"id":270309,"name":"Justin Taft","orcid":"0000-0002-9998-0429","position":5,"is_corresponding":false},{"id":629814,"name":"Ashley Richardson","orcid":"0000-0002-1700-9162","position":6,"is_corresponding":false},{"id":270307,"name":"Marta Martín-Fernández","orcid":"0000-0003-4671-6349","position":7,"is_corresponding":false},{"id":105284,"name":"Dusan Bogunovic","orcid":"0000-0002-9277-3232","position":8,"is_corresponding":false},{"id":16983,"name":"Priyanthi N.P. Gnanapragasam","orcid":null,"position":9,"is_corresponding":false},{"id":17000,"name":"Pamela J. Björkman","orcid":"0000-0002-2277-3990","position":10,"is_corresponding":false},{"id":700551,"name":"Patricia Spilman","orcid":"0000-0003-2626-6475","position":11,"is_corresponding":false},{"id":329582,"name":"Kayvan Niazi","orcid":"0000-0002-7098-1751","position":12,"is_corresponding":false},{"id":329581,"name":"Shahrooz Rabizadeh","orcid":"0000-0002-8609-7645","position":13,"is_corresponding":false},{"id":321139,"name":"Patrick Soon‐Shiong","orcid":"0000-0002-4682-8298","position":14,"is_corresponding":false},{"id":344043,"name":"Shiho Tanaka","orcid":"0000-0002-2562-9660","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:54:38.004707Z","pmid":"34545362","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":[]}