EMD-35747

Single-particle
3.79 Å
EMD-35747 Deposition: 26/03/2023
Map released: 16/08/2023
Last modified: 06/03/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-35747

cryo-EM structure of SARS-CoV-2 Omicron BA.2 spike protein in complex with double nAbs 8H12 and 3E2

EMD-35747

Single-particle
3.79 Å
EMD-35747 Deposition: 26/03/2023
Map released: 16/08/2023
Last modified: 06/03/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Severe acute respiratory syndrome coronavirus 2, Mus musculus
Sample: SARS-CoV-2 Omicron BA.2 spike protein in complex with double nAbs 8H12 and 3E2

Deposition Authors: Sun H , Jiang Y, Zheng Q , Li S , Xia N
Two antibodies show broad, synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD.
PUBMED: 37470320
DOI: doi:10.1093/procel/pwad040
ISSN: 1674-8018
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.