8D0Z

S728-1157 IgG in complex with SARS-CoV-2-6P-Mut7 Spike protein (focused refinement)

Summary for 8D0Z

• Entry DOI: 10.2210/pdb8d0z/pdb
• EMDB information: 27113
• Descriptor: Spike glycoprotein, S728-1157 Fab heavy chain variable region, S728-1157 Fab light chain variable region, ... (4 entities in total)
• Functional Keywords: sars-cov-2, cross-neutralizing antibody, neutralizing mab, variants of concern, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 5
• Total formula weight: 450291.76

Authors

Ozorowski, G.,Torres, J.L.,Ward, A.B. (deposition date: 2022-05-26, release date: 2023-03-22, Last modification date: 2024-10-23)

Primary citation

Changrob, S.,Halfmann, P.J.,Liu, H.,Torres, J.L.,McGrath, J.J.C.,Ozorowski, G.,Li, L.,Wilbanks, G.D.,Kuroda, M.,Maemura, T.,Huang, M.,Zheng, N.Y.,Turner, H.L.,Erickson, S.A.,Fu, Y.,Yasuhara, A.,Singh, G.,Monahan, B.,Mauldin, J.,Srivastava, K.,Simon, V.,Krammer, F.,Sather, D.N.,Ward, A.B.,Wilson, I.A.,Kawaoka, Y.,Wilson, P.C.
Site of vulnerability on SARS-CoV-2 spike induces broadly protective antibody against antigenically distinct Omicron subvariants.
J.Clin.Invest., 133:-, 2023

PubMed Abstract: The rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identified S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) that was derived from an individual previously infected with WT SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrated broad cross-neutralization of all dominant variants, including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.1/BA.2/BA.2.75/BA.4/BA.5/BL.1/XBB). Furthermore, S728-1157 protected hamsters against in vivo challenges with WT, Delta, and BA.1 viruses. Structural analysis showed that this antibody targets a class 1/RBS-A epitope in the receptor binding domain via multiple hydrophobic and polar interactions with its heavy chain complementarity determining region 3 (CDR-H3), in addition to common motifs in CDR-H1/CDR-H2 of class 1/RBS-A antibodies. Importantly, this epitope was more readily accessible in the open and prefusion state, or in the hexaproline (6P)-stabilized spike constructs, as compared with diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential and may inform target-driven vaccine designs against future SARS-CoV-2 variants.

PubMed: 36862518
DOI: 10.1172/JCI166844

Experimental method

ELECTRON MICROSCOPY (3.7 Å)