{"doi":"10.17615/nnhx-7h96","title":"Potent and Broad Neutralization of SARS-CoV-2 Variants of Concern (VOCs) including Omicron Sub-lineages BA.1 and BA.2 by Biparatopic Human VH Domains","abstract":"The emergence of SARS-CoV-2 variants of concern (VOCs) requires the development of next-generation biologics with high neutralization breadth. Here, we characterized a human VH domain, F6, which we generated by sequentially panning large phage displayed VH libraries against receptor binding domains (RBDs) containing VOC mutations. Cryo-EM analyses reveal that F6 has a unique binding mode that spans a broad surface of the RBD and involves the antibody framework region. Attachment of a Fc region to a fusion of F6 and ab8, a previously characterized VH domain, resulted in a construct (F6-ab8-Fc) that broadly and potently neutralized VOCs including Omicron. Additionally, prophylactic treatment using F6-ab8-Fc reduced live Beta (B.1.351) variant viral titers in the lungs of a mouse model. Our results provide a new potential therapeutic against SARS-CoV-2 variants including Omicron and highlight a vulnerable epitope within the spike that may be exploited to achieve broad protection against circulating variants.","journal":"UNC Libraries","year":2022,"id":310563,"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":0.958,"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":105112,"name":"Alexandra Schäfer","orcid":null,"position":1,"is_corresponding":false},{"id":856505,"name":"Michelle M. 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Castanha","orcid":"0000-0002-1220-5308","position":11,"is_corresponding":false},{"id":267224,"name":"Zehua Sun","orcid":"0000-0003-4287-1763","position":12,"is_corresponding":false},{"id":267228,"name":"Dhiraj Mannar","orcid":"0000-0002-7154-8677","position":13,"is_corresponding":false},{"id":5952,"name":"Ralph S. Baric","orcid":"0000-0001-6827-8701","position":14,"is_corresponding":false},{"id":765528,"name":"Cynthia Adams","orcid":"0000-0001-7688-8518","position":15,"is_corresponding":false},{"id":231568,"name":"Mary Hongying Cheng","orcid":"0000-0001-5833-8221","position":16,"is_corresponding":false},{"id":261178,"name":"Michele D. 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