7WHJ

The state 1 complex structure of Omicron spike with Bn03 (1-up RBD, 3 nanobodies)

Summary for 7WHJ

• Entry DOI: 10.2210/pdb7whj/pdb
• EMDB information: 32501
• Descriptor: Spike glycoprotein, Bn03_nano1, Bn03_nano2, ... (4 entities in total)
• Functional Keywords: omicron, spike, nanobody, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 6
• Total formula weight: 477927.71

Authors

Zhan, W.Q.,Zhang, X.,Chen, Z.G.,Sun, L. (deposition date: 2021-12-30, release date: 2022-05-11, Last modification date: 2024-11-13)

Primary citation

Li, C.,Zhan, W.,Yang, Z.,Tu, C.,Hu, G.,Zhang, X.,Song, W.,Du, S.,Zhu, Y.,Huang, K.,Kong, Y.,Zhang, M.,Mao, Q.,Gu, X.,Zhang, Y.,Xie, Y.,Deng, Q.,Song, Y.,Chen, Z.,Lu, L.,Jiang, S.,Wu, Y.,Sun, L.,Ying, T.
Broad neutralization of SARS-CoV-2 variants by an inhalable bispecific single-domain antibody.
Cell, 185:1389-1401.e18, 2022

PubMed Abstract: The effectiveness of SARS-CoV-2 vaccines and therapeutic antibodies have been limited by the continuous emergence of viral variants and by the restricted diffusion of antibodies from circulation into the sites of respiratory virus infection. Here, we report the identification of two highly conserved regions on the Omicron variant receptor-binding domain recognized by broadly neutralizing antibodies. Furthermore, we generated a bispecific single-domain antibody that was able to simultaneously and synergistically bind these two regions on a single Omicron variant receptor-binding domain as revealed by cryo-EM structures. We demonstrated that this bispecific antibody can be effectively delivered to lung via inhalation administration and exhibits exquisite neutralization breadth and therapeutic efficacy in mouse models of SARS-CoV-2 infections. Importantly, this study also deciphered an uncommon and highly conserved cryptic epitope within the spike trimeric interface that may have implications for the design of broadly protective SARS-CoV-2 vaccines and therapeutics.

PubMed: 35344711
DOI: 10.1016/j.cell.2022.03.009

Experimental method

ELECTRON MICROSCOPY (3.27 Å)