7X7U

Cryo-EM structure of SARS-CoV-2 Delta variant spike protein in complex with three nAbs X01, X10 and X17

Summary for 7X7U

• Entry DOI: 10.2210/pdb7x7u/pdb
• EMDB information: 33048
• Descriptor: Spike protein S1, X10 light chain, X10 heavy chain, ... (8 entities in total)
• Functional Keywords: sars-cov-2 delta variant, neutralizing antibody, cryo-em, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV,SARS-CoV-2); More
• Total number of polymer chains: 7
• Total formula weight: 98489.11

Authors

Sun, H.,Liu, L.,Zhang, T.,Zheng, Q.,Li, S.,Xia, N. (deposition date: 2022-03-10, release date: 2022-08-17, Last modification date: 2024-11-06)

Primary citation

Xiong, H.,Sun, H.,Wang, S.,Yuan, L.,Liu, L.,Zhu, Y.,Zhang, J.,Huang, Y.,Qi, R.,Jiang, Y.,Ma, J.,Zhou, M.,Ma, Y.,Fu, R.,Yan, S.,Yue, M.,Wu, Y.,Wei, M.,Wang, Y.,Li, T.,Wang, Y.,Zheng, Z.,Yu, H.,Cheng, T.,Li, S.,Yuan, Q.,Zhang, J.,Guan, Y.,Zheng, Q.,Zhang, T.,Xia, N.
The neutralizing breadth of antibodies targeting diverse conserved epitopes between SARS-CoV and SARS-CoV-2.
Proc.Natl.Acad.Sci.USA, 119:e2204256119-e2204256119, 2022

PubMed Abstract: Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of the potential candidates, we found that nAbs X01, X10, and X17 offer broad neutralizing potential against most variants of concern, with X17 further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-electron microscopy structures of the three antibodies together in complex with each of the spike proteins of the prototypical SARS-CoV, SARS-CoV-2, and Delta and Omicron variants of SARS-CoV-2 defined three nonoverlapping conserved epitopes on the receptor-binding domain. The triple-antibody mixture exhibited enhanced resistance to viral evasion and effective protection against infection of the Beta variant in hamsters. Our findings will aid the development of antibody therapeutics and broad vaccines against SARS-CoV-2 and its emerging variants.

PubMed: 35972965
DOI: 10.1073/pnas.2204256119

Experimental method

ELECTRON MICROSCOPY (3.77 Å)