biostudies-literatureSankhala RSNIAID NIH HHSNIGMS NIH HHS131-147.e7https://www.ebi.ac.uk/biostudies/studies/S-EPMC11145656biostudies-literatureUnknown32(2)Given the continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs), immunotherapeutics that target conserved epitopes on the spike (S) glycoprotein have therapeutic advantages. Here, we report the crystal structure of the SARS-CoV-2 S receptor-binding domain (RBD) at 1.95 Å and describe flexibility and distinct conformations of the angiotensin-converting enzyme 2 (ACE2)-binding site. We identify a set of SARS-CoV-2-reactive monoclonal antibodies (mAbs) with broad RBD cross-reactivity including SARS-CoV-2 Omicron subvariants, SARS-CoV-1, and other sarbecoviruses and determine the crystal structures of mAb-RBD complexes with Ab246 and CR3022 mAbs targeting the class IV site, WRAIR-2134, which binds the recently designated class V epitopeStructure (London, England : 1993)Antibody targeting of conserved sites of vulnerability on the SARS-CoV-2 spike receptor-binding domain.PMC11145656R01 AI155983P41 GM103403Peterson CESwafford ISankhala RSRolland MPolonis VRChoe MTran UGromowski GDKuklis CRajan SKing JDussupt VCurrier JRCorbitt CWieczorek LBai HLal KGde Val NYan Lvan Dyk DJoyce MGSmith CBroder CCZemil MTownsley SMMendez-Rivera LSterling SLEsser MTRees PAChang WCSoman SGreen ECJensen JLLaing EDBritton ZModjarrad KLoo YMChen WHKrebs SJHajduczki AMichael NLPaquin-Proulx DDonofrio GCMartinez EJMcTamney PMfalseAntibody targeting of conserved sites of vulnerability on the SARS-CoV-2 spike receptor-binding domain.Given the continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs), immunotherapeutics that target conserved epitopes on the spike (S) glycoprotein have therapeutic advantages. Here, we report the crystal structure of the SARS-CoV-2 S receptor-binding domain (RBD) at 1.95 Å and describe flexibility and distinct conformations of the angiotensin-converting enzyme 2 (ACE2)-binding site. We identify a set of SARS-CoV-2-reactive monoclonal antibodies (mAbs) with broad RBD cross-reactivity including SARS-CoV-2 Omicron subvariants, SARS-CoV-1, and other sarbecoviruses and determine the crystal structures of mAb-RBD complexes with Ab246 and CR3022 mAbs targeting the class IV site, WRAIR-2134, which binds the recently designated class V epitope2024-01-01T00:00:00Z2024 Feb2026-06-02T11:58:34.401Z2025-04-03T23:23:39.469ZS-EPMC111456563815785610.1016/j.str.2023.11.015