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Many of the variants cause breakthrough infections in vaccinated populations, posing great challenges to current antiviral strategies targeting the immunodominance of the receptor\u2010binding domain within the spike protein. Here, we found that a novel broadly neutralizing monoclonal antibody (mAb), G5, provided efficient protection against SARS\u2010CoV\u20102 variants of concern (VOCs) in vitro and in vivo. A single dose of mAb G5 could significantly inhibit the viral burden in mice challenged with the mouse\u2010adapted SARS\u2010CoV\u20102 or SARS\u2010CoV\u20102 Omicron BA.1 variant, as well as the body weight loss and cytokine release induced by mouse\u2010adapted SARS\u2010CoV\u20102. The refined epitope recognized by mAb G5 was identified as <jats:sub>1148<\/jats:sub>FKEELDKYF<jats:sub>1156<\/jats:sub> in the stem helix of subunit S2. In addition, a human\u2212mouse chimeric mAb was generated based on the variable region of heavy chain and VL genes of mAb G5. Our study provides a broad antibody drug candidate against SARS\u2010CoV\u20102 VOCs and reveals a novel target for developing pan\u2010SARS\u2010CoV\u20102 vaccines.<\/jats:p>","DOI":"10.1002\/jmv.28657","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T11:45:19Z","timestamp":1678707919000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel mAb broadly neutralizes SARS\u2010CoV\u20102 VOCs in vitro and in vivo, including the Omicron variants"],"prefix":"10.1002","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8348-9291","authenticated-orcid":false,"given":"Qiuqi","family":"Kan","sequence":"first","affiliation":[{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Yangzhou University  Yangzhou Jiangsu China"},{"name":"Key Laboratory of Jiangsu Preventive Veterinary Medicine, Key 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