7MW5

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

7MW5 の概要

• エントリーDOI: 10.2210/pdb7mw5/pdb
• EMDBエントリー: 24063
• 分子名称: Fab of antibody clone 2, light chain, Fab of antibody clone 2, heavy chain, Spike glycoprotein, ... (5 entities in total)
• 機能のキーワード: viral protein, antibody, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 614215.90

構造登録者

Hu, Y.,Xiong, Y. (登録日: 2021-05-15, 公開日: 2022-03-16, 最終更新日: 2025-05-28)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.42 Å)