{"doi":"10.17615/0cy8-md90","title":"A MERS-CoV antibody neutralizes a pre-emerging group 2c bat coronavirus","abstract":"The repeated emergence of zoonotic human betacoronaviruses (&beta;-CoVs) dictates the need for broad therapeutics and conserved epitope targets for countermeasure design. Middle East respiratory syndrome (MERS)-related coronaviruses (CoVs) remain a pressing concern for global health preparedness. Using metagenomic sequence data and CoV reverse genetics, we recovered a full-length wild-type MERS-like BtCoV/<em>li</em>/GD/2014-422 (BtCoV-422) recombinant virus, as well as two reporter viruses, and evaluated their human emergence potential and susceptibility to currently available countermeasures. Similar to MERS-CoV, BtCoV-422 efficiently used human and other mammalian dipeptidyl peptidase protein 4 (DPP4) proteins as entry receptors and an alternative DPP4-independent infection route in the presence of exogenous proteases. BtCoV-422 also replicated efficiently in primary human airway, lung endothelial, and fibroblast cells, although less efficiently than MERS-CoV. However, BtCoV-422 shows minor signs of infection in 288/330 human DPP4 transgenic mice. Several broad CoV antivirals, including nucleoside analogs and 3C-like/M<sup>pro</sup> protease inhibitors, demonstrated potent inhibition against BtCoV-422 in vitro. Serum from mice that received a MERS-CoV mRNA vaccine showed reduced neutralizing activity against BtCoV-422. Although most MERS-CoV-neutralizing monoclonal antibodies (mAbs) had limited activity, one anti-MERS receptor binding domain mAb, JC57-11, neutralized BtCoV-422 potently. A cryo-electron microscopy structure of JC57-11 in complex with BtCoV-422 spike protein revealed the mechanism of cross-neutralization involving occlusion of the DPP4 binding site, highlighting its potential as a broadly neutralizing mAb for group 2c CoVs that use DPP4 as a receptor. These studies provide critical insights into MERS-like CoVs and provide candidates for countermeasure development.","journal":"UNC Libraries","year":2025,"id":560086,"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":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105588,"name":"Lingshu Wang","orcid":"0000-0002-8404-4910","position":1,"is_corresponding":false},{"id":72632,"name":"Scott H. 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Yount","orcid":"0000-0002-6099-8429","position":11,"is_corresponding":false},{"id":277822,"name":"Rita M. Meganck","orcid":"0000-0003-2799-3754","position":12,"is_corresponding":false},{"id":5947,"name":"Yixuan J. Hou","orcid":"0000-0002-8323-7243","position":13,"is_corresponding":false},{"id":105504,"name":"Teresa Mascenik","orcid":"0000-0002-9694-756X","position":14,"is_corresponding":false},{"id":105112,"name":"Alexandra Schäfer","orcid":null,"position":15,"is_corresponding":false},{"id":105111,"name":"Sarah R. Leist","orcid":"0000-0002-4989-5381","position":16,"is_corresponding":false},{"id":105502,"name":"Rhianna E. Lee","orcid":"0000-0003-2039-1304","position":17,"is_corresponding":false},{"id":87312,"name":"Jason S. McLellan","orcid":"0000-0003-3991-542X","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:55:39.010633Z","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":[]}