7CYV
Crystal structure of FD20, a neutralizing single-chain variable fragment (scFv) in complex with SARS-CoV-2 Spike receptor-binding domain (RBD)
Summary for 7CYV
| Entry DOI | 10.2210/pdb7cyv/pdb |
| Descriptor | The heavy chain variable region of the scFv FD20,The light chain variable region of the scFv FD20, Spike protein S1, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-3)][alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
| Functional Keywords | coronavirus, covid-19, ncov-2019, neutralizing antibody, receptor-binding domain, sars-cov-2, scfv, single-chain variable fragment, spike, viral protein |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 2 |
| Total formula weight | 54319.98 |
| Authors | |
| Primary citation | Li, T.,Cai, H.,Zhao, Y.,Li, Y.,Lai, Y.,Yao, H.,Liu, L.D.,Sun, Z.,van Vlissingen, M.F.,Kuiken, T.,GeurtsvanKessel, C.H.,Zhang, N.,Zhou, B.,Lu, L.,Gong, Y.,Qin, W.,Mondal, M.,Duan, B.,Xu, S.,Richard, A.S.,Raoul, H.,Chen, J.,Xu, C.,Wu, L.,Zhou, H.,Huang, Z.,Zhang, X.,Li, J.,Wang, Y.,Bi, Y.,Rockx, B.,Chen, J.,Meng, F.L.,Lavillette, D.,Li, D. Uncovering a conserved vulnerability site in SARS-CoV-2 by a human antibody. Embo Mol Med, 13:e14544-e14544, 2021 Cited by PubMed Abstract: An essential step for SARS-CoV-2 infection is the attachment to the host cell receptor by its Spike receptor-binding domain (RBD). Most of the existing RBD-targeting neutralizing antibodies block the receptor-binding motif (RBM), a mutable region with the potential to generate neutralization escape mutants. Here, we isolated and structurally characterized a non-RBM-targeting monoclonal antibody (FD20) from convalescent patients. FD20 engages the RBD at an epitope distal to the RBM with a K of 5.6 nM, neutralizes SARS-CoV-2 including the current Variants of Concern such as B.1.1.7, B.1.351, P.1, and B.1.617.2 (Delta), displays modest cross-reactivity against SARS-CoV, and reduces viral replication in hamsters. The epitope coincides with a predicted "ideal" vulnerability site with high functional and structural constraints. Mutation of the residues of the conserved epitope variably affects FD20-binding but confers little or no resistance to neutralization. Finally, in vitro mode-of-action characterization and negative-stain electron microscopy suggest a neutralization mechanism by which FD20 destructs the Spike. Our results reveal a conserved vulnerability site in the SARS-CoV-2 Spike for the development of potential antiviral drugs. PubMed: 34672091DOI: 10.15252/emmm.202114544 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.13 Å) |
Structure validation
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