7RU3

CC6.33 IgG in complex with SARS-CoV-2-6P-Mut7 S protein (non-uniform refinement)

Summary for 7RU3

• Entry DOI: 10.2210/pdb7ru3/pdb
• EMDB information: 24695
• Descriptor: CC6.33 IgG heavy chain Fv, CC6.33 IgG Kappa chain Fv, Spike glycoprotein, ... (6 entities in total)
• Functional Keywords: covid, sars-cov-2, stabilizing mutations, neutralizing antibody, rbd, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 7
• Total formula weight: 482021.43

Authors

Ozorowski, G.,Turner, H.L.,Ward, A.B. (deposition date: 2021-08-16, release date: 2022-08-24, Last modification date: 2025-05-14)

Primary citation

Zhao, F.,Keating, C.,Ozorowski, G.,Shaabani, N.,Francino-Urdaniz, I.M.,Barman, S.,Limbo, O.,Burns, A.,Zhou, P.,Ricciardi, M.J.,Woehl, J.,Tran, Q.,Turner, H.L.,Peng, L.,Huang, D.,Nemazee, D.,Andrabi, R.,Sok, D.,Teijaro, J.R.,Whitehead, T.A.,Ward, A.B.,Burton, D.R.,Jardine, J.G.
Engineering SARS-CoV-2 neutralizing antibodies for increased potency and reduced viral escape pathways.
Iscience, 25:104914-104914, 2022

PubMed Abstract: The rapid spread of SARS-CoV-2 variants poses a constant threat of escape from monoclonal antibody and vaccine countermeasures. Mutations in the ACE2 receptor binding site on the surface S protein have been shown to disrupt antibody binding and prevent viral neutralization. Here, we used a directed evolution-based approach to engineer three neutralizing antibodies for enhanced binding to S protein. The engineered antibodies showed increased functional activity in terms of neutralization potency and/or breadth of neutralization against viral variants. Deep mutational scanning revealed that higher binding affinity reduces the total number of viral escape mutations. Studies in the Syrian hamster model showed two examples where the affinity-matured antibody provided superior protection compared to the parental antibody. These data suggest that monoclonal antibodies for antiviral indications would benefit from affinity maturation to reduce viral escape pathways and appropriate affinity maturation in vaccine immunization could help resist viral variation.

PubMed: 35971553
DOI: 10.1016/j.isci.2022.104914

Experimental method

ELECTRON MICROSCOPY (3.3 Å)