8KER

Structure of SARS-CoV-2 XBB Variant Spike protein complexed with broadly neutralizing antibody PW5-535

Summary for 8KER

• Entry DOI: 10.2210/pdb8ker/pdb
• EMDB information: 37165
• Descriptor: Spike glycoprotein, PW5-535 light chain, PW5-535 heavy chain (3 entities in total)
• Functional Keywords: antibody, viral protein, immune system-viral protein complex, immune system/viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 9
• Total formula weight: 647970.46

Authors

Sun, L.,Mao, Q.,Wang, Y. (deposition date: 2023-08-13, release date: 2024-08-14, Last modification date: 2024-11-13)

Primary citation

Zhao, X.,Qiu, T.,Huang, X.,Mao, Q.,Wang, Y.,Qiao, R.,Li, J.,Mao, T.,Wang, Y.,Cun, Y.,Wang, C.,Luo, C.,Yoon, C.,Wang, X.,Li, C.,Cui, Y.,Zhao, C.,Li, M.,Chen, Y.,Cai, G.,Geng, W.,Hu, Z.,Cao, J.,Zhang, W.,Cao, Z.,Chu, H.,Sun, L.,Wang, P.
Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination.
Cell Discov, 10:14-14, 2024

PubMed Abstract: The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the need to develop antivirals against SARS-CoV-2 and related sarbecoviruses. Here, we identified both potent and broadly neutralizing antibodies from a five-dose vaccinated donor who exhibited cross-reactive serum-neutralizing activity against diverse coronaviruses. Through single B-cell sorting and sequencing followed by a tailor-made computational pipeline, we successfully selected 86 antibodies with potential cross-neutralizing ability from 684 antibody sequences. Among them, PW5-570 potently neutralized all SARS-CoV-2 variants that arose prior to Omicron BA.5, and the other three could broadly neutralize all current SARS-CoV-2 variants of concern, SARS-CoV and their related sarbecoviruses (Pangolin-GD, RaTG13, WIV-1, and SHC014). Cryo-EM analysis demonstrates that these antibodies have diverse neutralization mechanisms, such as disassembling spike trimers, or binding to RBM or SD1 to affect ACE2 binding. In addition, prophylactic administration of these antibodies significantly protects nasal turbinate and lung infections against BA.1, XBB.1, and SARS-CoV viral challenge in golden Syrian hamsters, respectively. Importantly, post-exposure treatment with PW5-5 and PW5-535 also markedly protects against XBB.1 challenge in these models. This study reveals the potential utility of computational process to assist screening cross-reactive antibodies, as well as the potency of vaccine-induced broadly neutralizing antibodies against current SARS-CoV-2 variants and related sarbecoviruses, offering promising avenues for the development of broad therapeutic antibody drugs.

PubMed: 38320990
DOI: 10.1038/s41421-024-00648-1

Experimental method

ELECTRON MICROSCOPY (2.95 Å)