8FXC

SARS-CoV-2 BQ.1.1 spike RBD bound to the human ACE2 ectodomain and the S309 neutralizing antibody Fab fragment

Summary for 8FXC

• Entry DOI: 10.2210/pdb8fxc/pdb
• EMDB information: 29531
• Descriptor: S309 Light chain, S309 Heavy chain, Processed angiotensin-converting enzyme 2, ... (7 entities in total)
• Functional Keywords: sars-cov-2, covid-19, bq.1.1, spike glycoprotein, neutralizing antibodies, structural genomics, seattle structural genomics center for infectious disease, ssgcid, inhibitor, ace2, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 177596.08

Authors

Park, Y.J.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Veesler, D. (deposition date: 2023-01-24, release date: 2023-10-04, Last modification date: 2024-10-16)

Primary citation

Addetia, A.,Piccoli, L.,Case, J.B.,Park, Y.J.,Beltramello, M.,Guarino, B.,Dang, H.,de Melo, G.D.,Pinto, D.,Sprouse, K.,Scheaffer, S.M.,Bassi, J.,Silacci-Fregni, C.,Muoio, F.,Dini, M.,Vincenzetti, L.,Acosta, R.,Johnson, D.,Subramanian, S.,Saliba, C.,Giurdanella, M.,Lombardo, G.,Leoni, G.,Culap, K.,McAlister, C.,Rajesh, A.,Dellota Jr., E.,Zhou, J.,Farhat, N.,Bohan, D.,Noack, J.,Chen, A.,Lempp, F.A.,Quispe, J.,Kergoat, L.,Larrous, F.,Cameroni, E.,Whitener, B.,Giannini, O.,Cippa, P.,Ceschi, A.,Ferrari, P.,Franzetti-Pellanda, A.,Biggiogero, M.,Garzoni, C.,Zappi, S.,Bernasconi, L.,Kim, M.J.,Rosen, L.E.,Schnell, G.,Czudnochowski, N.,Benigni, F.,Franko, N.,Logue, J.K.,Yoshiyama, C.,Stewart, C.,Chu, H.,Bourhy, H.,Schmid, M.A.,Purcell, L.A.,Snell, G.,Lanzavecchia, A.,Diamond, M.S.,Corti, D.,Veesler, D.
Neutralization, effector function and immune imprinting of Omicron variants.
Nature, 621:592-601, 2023

PubMed Abstract: Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain (RBD) of the spike protein. The effects of these mutations on viral infection and transmission and the efficacy of vaccines and therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 and XBB.1.5 variants bind host ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1, XBB.1 and BN.1 RBDs bound to the fragment antigen-binding region of the S309 antibody (the parent antibody for sotrovimab) and human ACE2 explain the preservation of antibody binding through conformational selection, altered ACE2 recognition and immune evasion. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1 and hamsters challenged with XBB.1.5. Vaccine-elicited human plasma antibodies cross-react with and trigger effector functions against current Omicron variants, despite a reduced neutralizing activity, suggesting a mechanism of protection against disease, exemplified by S309. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring the role of persistent immune imprinting.

PubMed: 37648855
DOI: 10.1038/s41586-023-06487-6

Experimental method

ELECTRON MICROSCOPY (3.2 Å)