7FBK

Crystal structure of SARS-CoV-2 receptor binding domain N501Y mutant in complex with neutralizing nanobody 20G6

Summary for 7FBK

• Entry DOI: 10.2210/pdb7fbk/pdb
• Descriptor: Spike protein S1, New antigen receptor variable domain, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: sars-cov-2, spike glycoprotein, rbd, vnar, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 4
• Total formula weight: 81267.94

Authors

Zhu, J.,Xu, T.,Feng, B.,Liu, J. (deposition date: 2021-07-11, release date: 2022-07-13, Last modification date: 2024-11-06)

Primary citation

Feng, B.,Chen, Z.,Sun, J.,Xu, T.,Wang, Q.,Yi, H.,Niu, X.,Zhu, J.,Fan, M.,Hou, R.,Shao, Y.,Huang, S.,Li, C.,Hu, P.,Zheng, P.,He, P.,Luo, J.,Yan, Q.,Xiong, X.,Liu, J.,Zhao, J.,Chen, L.
A Class of Shark-Derived Single-Domain Antibodies can Broadly Neutralize SARS-Related Coronaviruses and the Structural Basis of Neutralization and Omicron Escape.
Small Methods, 6:e2200387-e2200387, 2022

PubMed Abstract: The identification of a novel class of shark-derived single domain antibodies, named vnarbodies that show picomolar affinities binding to the receptor binding domain (RBD) of Wuhan and Alpha, Beta, Kappa, Delta, Delta-plus, and Lambda variants, is reported. Vnarbody 20G6 and 17F6 have broad neutralizing activities against all these SARS-CoV-2 viruses as well as other sarbecoviruses, including Pangolin coronavirus and Bat coronavirus. Intranasal administration of 20G6 effectively protects mice from the challenges of SARS-CoV-2 Wuhan and Beta variants. 20G6 and 17F6 contain a unique "WXGY" motif in the complementary determining region 3 that binds to a hidden epitope on RBD, which is highly conserved in sarbecoviruses through a novel β-sheet interaction. It is found that the S375F mutation on Omicron RBD disrupts the structure of β-strand, thus impair the binding with 20G6. The study demonstrates that shark-derived vnarbodies offer a prophylactic and therapeutic option against most SARS-CoV-2 variants and provide insights into antibody evasion by the Omicron variant.

PubMed: 35583124
DOI: 10.1002/smtd.202200387

Experimental method

X-RAY DIFFRACTION (1.9 Å)