7CYV

Crystal structure of FD20, a neutralizing single-chain variable fragment (scFv) in complex with SARS-CoV-2 Spike receptor-binding domain (RBD)

7CYV の概要

• エントリーDOI: 10.2210/pdb7cyv/pdb
• 分子名称: 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)
• 機能のキーワード: coronavirus, covid-19, ncov-2019, neutralizing antibody, receptor-binding domain, sars-cov-2, scfv, single-chain variable fragment, spike, viral protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 54319.98

構造登録者

Li, Y.,Li, T.,Lai, Y.,Cai, H.,Yao, H.,Li, D. (登録日: 2020-09-04, 公開日: 2021-09-15, 最終更新日: 2024-10-09)

主引用文献

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

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: 34672091
DOI: 10.15252/emmm.202114544

実験手法

X-RAY DIFFRACTION (3.13 Å)