8IVA

Cryo-EM structure of SARS-CoV-2 spike protein in complex with double nAbs XMA01 and 3E2 (local refinement)

Summary for 8IVA

• Entry DOI: 10.2210/pdb8iva/pdb
• EMDB information: 35755
• Descriptor: heavy chain of XMA01, light chain of XMA01, Spike protein S1, ... (6 entities in total)
• Functional Keywords: sars-cov-2, neutralizing antibody, cryo-em, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 5
• Total formula weight: 72643.84

Authors

Sun, H.,Jiang, Y.,Zheng, Q.,Li, S.,Xia, N. (deposition date: 2023-03-26, release date: 2023-08-16, Last modification date: 2024-11-20)

Primary citation

Sun, H.,Deng, T.,Zhang, Y.,Lin, Y.,Jiang, Y.,Jiang, Y.,Huang, Y.,Song, S.,Cui, L.,Li, T.,Xiong, H.,Lan, M.,Liu, L.,Li, Y.,Fang, Q.,Yu, K.,Jiang, W.,Zhou, L.,Que, Y.,Zhang, T.,Yuan, Q.,Cheng, T.,Zhang, Z.,Yu, H.,Zhang, J.,Luo, W.,Li, S.,Zheng, Q.,Gu, Y.,Xia, N.
Two antibodies show broad, synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD.
Protein Cell, 15:121-134, 2024

PubMed Abstract: Continual evolution of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus has allowed for its gradual evasion of neutralizing antibodies (nAbs) produced in response to natural infection or vaccination. The rapid nature of these changes has incited a need for the development of superior broad nAbs (bnAbs) and/or the rational design of an antibody cocktail that can protect against the mutated virus strain. Here, we report two angiotensin-converting enzyme 2 competing nAbs-8H12 and 3E2-with synergistic neutralization but evaded by some Omicron subvariants. Cryo-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric clashing. Bispecific antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant XBB.1.5. Together, these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.

PubMed: 37470320
DOI: 10.1093/procel/pwad040

Experimental method

ELECTRON MICROSCOPY (3.95 Å)