7MW4

Structure of the SARS-CoV-2 Spike trimer with one RBD down in complex with the Fab fragment of human neutralizing antibody clone 6

Summary for 7MW4

• Entry DOI: 10.2210/pdb7mw4/pdb
• EMDB information: 24062
• Descriptor: Spike glycoprotein, Fab of antibody clone 6, light chain, Fab of antibody clone 6, heavy chain, ... (6 entities in total)
• Functional Keywords: 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: 9
• Total formula weight: 597408.65

Authors

Hu, Y.,Xiong, Y. (deposition date: 2021-05-15, release date: 2022-03-16, Last modification date: 2024-11-13)

Primary citation

Peng, L.,Hu, Y.,Mankowski, M.C.,Ren, P.,Chen, R.E.,Wei, J.,Zhao, M.,Li, T.,Tripler, T.,Ye, L.,Chow, R.D.,Fang, Z.,Wu, C.,Dong, M.B.,Cook, M.,Wang, G.,Clark, P.,Nelson, B.,Klein, D.,Sutton, R.,Diamond, M.S.,Wilen, C.B.,Xiong, Y.,Chen, S.
Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617.
Nat Commun, 13:1638-1638, 2022

PubMed Abstract: COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identify two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generate a bispecific antibody. Lead antibodies show strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solve several cryo-EM structures at ~3 Å resolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and reveal distinct epitopes, binding patterns, and conformations. The lead clones also show potent efficacy in vivo against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generate and characterize a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants.

PubMed: 35347138
DOI: 10.1038/s41467-022-29288-3

Experimental method

ELECTRON MICROSCOPY (3.42 Å)