7WQV

Crystal structure of a neutralizing monoclonal antibody (Ab08) in complex with SARS-CoV-2 receptor-binding domain (RBD)

Summary for 7WQV

• Entry DOI: 10.2210/pdb7wqv/pdb
• Descriptor: Spike protein S1, Ab08, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: ab08, mab, coronavirus, covid-19, monoclonal antibody, nab, neutralizing antibody, rbd, receptor-binding domain, sars-cov-2, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 16
• Total formula weight: 463813.98

Authors

Zha, J.,Meng, L.,Zhang, X.,Li, D. (deposition date: 2022-01-26, release date: 2023-01-25, Last modification date: 2024-10-16)

Primary citation

Meng, L.,Zha, J.,Zhou, B.,Cao, L.,Jiang, C.,Zhu, Y.,Li, T.,Lu, L.,Zhang, J.,Yang, H.,Feng, J.,Gu, Z.,Tang, H.,Jiang, L.,Li, D.,Lavillette, D.,Zhang, X.
A Spike-destructing human antibody effectively neutralizes Omicron-included SARS-CoV-2 variants with therapeutic efficacy.
Plos Pathog., 19:e1011085-e1011085, 2023

PubMed Abstract: Neutralizing antibodies (nAbs) are important assets to fight COVID-19, but most existing nAbs lose the activities against Omicron subvariants. Here, we report a human monoclonal antibody (Ab08) isolated from a convalescent patient infected with the prototype strain (Wuhan-Hu-1). Ab08 binds to the receptor-binding domain (RBD) with pico-molar affinity (230 pM), effectively neutralizes SARS-CoV-2 and variants of concern (VOCs) including Alpha, Beta, Gamma, Mu, Omicron BA.1 and BA.2, and to a lesser extent for Delta and Omicron BA.4/BA.5 which bear the L452R mutation. Of medical importance, Ab08 shows therapeutic efficacy in SARS-CoV-2-infected hACE2 mice. X-ray crystallography of the Ab08-RBD complex reveals an antibody footprint largely in the β-strand core and away from the ACE2-binding motif. Negative staining electron-microscopy suggests a neutralizing mechanism through which Ab08 destructs the Spike trimer. Together, our work identifies a nAb with therapeutic potential for COVID-19.

PubMed: 36706160
DOI: 10.1371/journal.ppat.1011085

Experimental method

X-RAY DIFFRACTION (2.8 Å)