7WDF

SARS-CoV-2 Beta spike in complex with two S3H3 Fabs

Summary for 7WDF

• Entry DOI: 10.2210/pdb7wdf/pdb
• EMDB information: 32437
• Descriptor: Spike glycoprotein, Heavy chain of S3H3 Fab, Light chain of S3H3 Fab (3 entities in total)
• Functional Keywords: sars-cov-2, coronavirus, beta variant, b.1.351 lineage, spike protein, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 7
• Total formula weight: 513270.79

Authors

Wang, Y.F.,Cong, Y. (deposition date: 2021-12-21, release date: 2022-02-02, Last modification date: 2024-10-23)

Primary citation

Xu, S.,Wang, Y.,Wang, Y.,Zhang, C.,Hong, Q.,Gu, C.,Xu, R.,Wang, T.,Yang, Y.,Zang, J.,Zhou, Y.,Li, Z.,Liu, Q.,Zhou, B.,Bai, L.,Zhu, Y.,Deng, Q.,Wang, H.,Lavillette, D.,Wong, G.,Xie, Y.,Cong, Y.,Huang, Z.
Mapping cross-variant neutralizing sites on the SARS-CoV-2 spike protein.
Emerg Microbes Infect, 11:351-367, 2022

PubMed Abstract: The emergence of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern threatens the efficacy of currently approved vaccines and authorized therapeutic monoclonal antibodies (MAbs). It is hence important to continue searching for SARS-CoV-2 broadly neutralizing MAbs and defining their epitopes. Here, we isolate 9 neutralizing mouse MAbs raised against the spike protein of a SARS-CoV-2 prototype strain and evaluate their neutralizing potency towards a panel of variants, including B.1.1.7, B.1.351, B.1.617.1, and B.1.617.2. By using a combination of biochemical, virological, and cryo-EM structural analyses, we identify three types of cross-variant neutralizing MAbs, represented by S5D2, S5G2, and S3H3, respectively, and further define their epitopes. S5D2 binds the top lateral edge of the receptor-binding motif within the receptor-binding domain (RBD) with a binding footprint centred around the loop, and efficiently neutralizes all variant pseudoviruses, but the potency against B.1.617.2 was observed to decrease significantly. S5G2 targets the highly conserved RBD core region and exhibits comparable neutralization towards the variant panel. S3H3 binds a previously unreported epitope located within the evolutionarily stable SD1 region and is able to near equally neutralize all of the variants tested. Our work thus defines three distinct cross-variant neutralizing sites on the SARS-CoV-2 spike protein, providing guidance for design and development of broadly effective vaccines and MAb-based therapies.

PubMed: 34964428
DOI: 10.1080/22221751.2021.2024455

Experimental method

ELECTRON MICROSCOPY (3.9 Å)