7cyv

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

spinqualitylabelsall models 7cyv, resolution 3.13Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7cyv is a 2 chain structure with sequence from Homo sapiens and Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.13Å Ligands: BMA, FUC, NAG, TPO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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(D) 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. Uncovering a conserved vulnerability site in SARS-CoV-2 by a human antibody.,Li T, Cai H, Zhao Y, Li Y, Lai Y, Yao H, Liu LD, Sun Z, van Vlissingen MF, Kuiken T, GeurtsvanKessel CH, Zhang N, Zhou B, Lu L, Gong Y, Qin W, Mondal M, Duan B, Xu S, Richard AS, 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 FL, Lavillette D, Li D EMBO Mol Med. 2021 Dec 7;13(12):e14544. doi: 10.15252/emmm.202114544. Epub 2021 , Nov 17. PMID:34672091 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures Monoclonal Antibodies 3D structures Spike protein 3D structures

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