7WS6

Structures of Omicron Spike complexes illuminate broad-spectrum neutralizing antibody development

Summary for 7WS6

• Entry DOI: 10.2210/pdb7ws6/pdb
• EMDB information: 32748
• Descriptor: Spike protein S1, 510A5 light chain, 510A5 heavy chain (3 entities in total)
• Functional Keywords: covid-19, spike glycoprotein, virus, viral protein, antibody, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 3
• Total formula weight: 50248.27

Authors

Guo, H.,Gao, Y.,Ji, X.,Yang, H. (deposition date: 2022-01-28, release date: 2022-06-01, Last modification date: 2024-10-23)

Primary citation

Guo, H.,Gao, Y.,Li, T.,Li, T.,Lu, Y.,Zheng, L.,Liu, Y.,Yang, T.,Luo, F.,Song, S.,Wang, W.,Yang, X.,Nguyen, H.C.,Zhang, H.,Huang, A.,Jin, A.,Yang, H.,Rao, Z.,Ji, X.
Structures of Omicron spike complexes and implications for neutralizing antibody development.
Cell Rep, 39:110770-110770, 2022

PubMed Abstract: The emergence of the SARS-CoV-2 Omicron variant is dominant in many countries worldwide. The high number of spike mutations is responsible for the broad immune evasion from existing vaccines and antibody drugs. To understand this, we first present the cryo-electron microscopy structure of ACE2-bound SARS-CoV-2 Omicron spike. Comparison to previous spike antibody structures explains how Omicron escapes these therapeutics. Secondly, we report structures of Omicron, Delta, and wild-type spikes bound to a patient-derived Fab antibody fragment (510A5), which provides direct evidence where antibody binding is greatly attenuated by the Omicron mutations, freeing spike to bind ACE2. Together with biochemical binding and 510A5 neutralization assays, our work establishes principles of binding required for neutralization and clearly illustrates how the mutations lead to antibody evasion yet retain strong ACE2 interactions. Structural information on spike with both bound and unbound antibodies collectively elucidates potential strategies for generation of therapeutic antibodies.

PubMed: 35477022
DOI: 10.1016/j.celrep.2022.110770

Experimental method

ELECTRON MICROSCOPY (3.8 Å)