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Using metagenomic sequence data and CoV reverse genetics, we recovered a full-length wild-type MERS-like BtCoV\/\n                    <jats:italic>li<\/jats:italic>\n                    \/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\n                    <jats:sup>pro<\/jats:sup>\n                    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\u2013neutralizing monoclonal antibodies (mAbs) had limited activity, one anti-MERS receptor binding domain mAb, JC57-11, neutralized BtCoV-422 potently. A cryo\u2013electron 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.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adg5567","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T13:58:48Z","timestamp":1695823128000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":39,"title":["A MERS-CoV antibody neutralizes a pre-emerging group 2c bat coronavirus"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7582-8396","authenticated-orcid":true,"given":"Longping V.","family":"Tse","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Saint Louis University, St.\u00a0Louis, MO 63014, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8323-7243","authenticated-orcid":true,"given":"Yixuan 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