7E3O

Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibody nCoV617

Summary for 7E3O

• Entry DOI: 10.2210/pdb7e3o/pdb
• Descriptor: nCoV617 Light Chain, nCoV617 Heigh Chain, Spike protein S1, ... (4 entities in total)
• Functional Keywords: sars-cov-2, s-rbd, rbs-c, native human monoclonal antibody, therapeutic antibody, viral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 69377.34

Authors

Chen, S.D.,Yang, M. (deposition date: 2021-02-09, release date: 2021-09-15, Last modification date: 2024-11-06)

Primary citation

Yang, M.,Li, J.,Huang, Z.,Li, H.,Wang, Y.,Wang, X.,Kang, S.,Huang, X.,Wu, C.,Liu, T.,Jia, Z.,Liang, J.,Yuan, X.,He, S.,Chen, X.,Zhou, Z.,Chen, Q.,Liu, S.,Li, J.,Zheng, H.,Liu, X.,Li, K.,Yao, X.,Lang, B.,Liu, L.,Liao, H.X.,Chen, S.
Structural Basis of a Human Neutralizing Antibody Specific to the SARS-CoV-2 Spike Protein Receptor-Binding Domain.
Microbiol Spectr, 9:e0135221-e0135221, 2021

PubMed Abstract: The emerging new lineages of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have marked a new phase of coronavirus disease 2019 (COVID-19). Understanding the recognition mechanisms of potent neutralizing monoclonal antibodies (NAbs) against the spike protein is pivotal for developing new vaccines and antibody drugs. Here, we isolated several monoclonal antibodies (MAbs) against the SARS-CoV-2 spike protein receptor-binding domain (S-RBD) from the B cell receptor repertoires of a SARS-CoV-2 convalescent. Among these MAbs, the antibody nCoV617 demonstrates the most potent neutralizing activity against authentic SARS-CoV-2 infection, as well as prophylactic and therapeutic efficacies against the human angiotensin-converting enzyme 2 (ACE2) transgenic mouse model . The crystal structure of S-RBD in complex with nCoV617 reveals that nCoV617 mainly binds to the back of the "ridge" of RBD and shares limited binding residues with ACE2. Under the background of the S-trimer model, it potentially binds to both "up" and "down" conformations of S-RBD. mutagenesis assays show that mutant residues found in the emerging new lineage B.1.1.7 of SARS-CoV-2 do not affect nCoV617 binding to the S-RBD. These results provide a new human-sourced neutralizing antibody against the S-RBD and assist vaccine development. COVID-19 is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic has posed a serious threat to global health and the economy, so it is necessary to find safe and effective antibody drugs and treatments. The receptor-binding domain (RBD) in the SARS-CoV-2 spike protein is responsible for binding to the angiotensin-converting enzyme 2 (ACE2) receptor. It contains a variety of dominant neutralizing epitopes and is an important antigen for the development of new coronavirus antibodies. The significance of our research lies in the determination of new epitopes, the discovery of antibodies against RBD, and the evaluation of the antibodies' neutralizing effect. The identified antibodies here may be drug candidates for the development of clinical interventions for SARS-CoV-2.

PubMed: 34643438
DOI: 10.1128/Spectrum.01352-21

Experimental method

X-RAY DIFFRACTION (2.51 Å)