8KHC

SARS-CoV-2 Omicron spike in complex with 5817 Fab

Summary for 8KHC

• Entry DOI: 10.2210/pdb8khc/pdb
• EMDB information: 37240
• Descriptor: Spike glycoprotein, Heavy chain of 5817 Fab, Light chain of 5817 Fab, ... (6 entities in total)
• Functional Keywords: sars-cov-2, omicron, rbd, fab, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 7
• Total formula weight: 432169.86

Authors

Cao, L.,Wang, X. (deposition date: 2023-08-21, release date: 2024-04-17, Last modification date: 2024-11-13)

Primary citation

Wang, Y.,Zhang, Z.,Yang, M.,Xiong, X.,Yan, Q.,Cao, L.,Wei, P.,Zhang, Y.,Zhang, L.,Lv, K.,Chen, J.,Liu, X.,Zhao, X.,Xiao, J.,Zhang, S.,Zhu, A.,Gan, M.,Zhang, J.,Cai, R.,Zhuo, J.,Zhang, Y.,Rao, H.,Qu, B.,Zhang, Y.,Chen, L.,Dai, J.,Cheng, L.,Hu, Q.,Chen, Y.,Lv, H.,So, R.T.Y.,Peiris, M.,Zhao, J.,Liu, X.,Mok, C.K.P.,Wang, X.,Zhao, J.
Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain.
Cell Rep, 43:113653-113653, 2024

PubMed Abstract: Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, which has broad-spectrum neutralization capacity against SARS-CoV-2 variants of concern (VOCs) and SARS-CoV, as well as related bat and pangolin viruses. 5817 can hardly compete with six classes of receptor-binding-domain-targeted antibodies grouped by structural classifications. No obvious impairment in the potency is detected against SARS-CoV-2 Omicron and subvariants. The cryoelectron microscopy (cryo-EM) structure of neutralizing antibody 5817 in complex with Omicron spike reveals a highly conserved epitope, only existing at the receptor-binding domain (RBD) open state. Prophylactic and therapeutic administration of 5817 potently protects mice from SARS-CoV-2 Beta, Delta, Omicron, and SARS-CoV infection. This study reveals a highly conserved cryptic epitope targeted by a broad sarbecovirus neutralizing antibody, which would be beneficial to meet the potential threat of pre-emergent SARS-CoV-2 VOCs.

PubMed: 38175758
DOI: 10.1016/j.celrep.2023.113653

Experimental method

ELECTRON MICROSCOPY (3 Å)