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Here, we identified a receptor-blocking human monoclonal antibody, 87G7, that retained potent in vitro neutralizing activity against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta, and Omicron (BA.1\/BA.2) VOCs. Using cryo\u2013electron microscopy and site-directed mutagenesis experiments, we showed that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protected mice and hamsters prophylactically against challenge with all current SARS-CoV-2 VOCs and showed therapeutic activity against SARS-CoV-2 challenge in both animal models. Our findings demonstrate that 87G7 holds promise as a prophylactic or therapeutic agent for COVID-19 that is more resilient to SARS-CoV-2 antigenic diversity.<\/jats:p>","DOI":"10.1126\/sciimmunol.abp9312","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T13:57:42Z","timestamp":1650981462000},"source":"Crossref","is-referenced-by-count":55,"title":["An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern"],"prefix":"10.1126","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0790-9546","authenticated-orcid":true,"given":"Wenjuan","family":"Du","sequence":"first","affiliation":[{"name":"Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 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