7SPO

Crystal structure of the SARS-CoV-2 receptor binding domain in complex with VNAR 3B4

Summary for 7SPO

• Entry DOI: 10.2210/pdb7spo/pdb
• Descriptor: Spike protein S1, VNAR 3B4, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 4
• Total formula weight: 80797.89

Authors

Shi, K.,Aihara, H. (deposition date: 2021-11-02, release date: 2022-01-05, Last modification date: 2024-11-06)

Primary citation

Ubah, O.C.,Lake, E.W.,Gunaratne, G.S.,Gallant, J.P.,Fernie, M.,Robertson, A.J.,Marchant, J.S.,Bold, T.D.,Langlois, R.A.,Matchett, W.E.,Thiede, J.M.,Shi, K.,Yin, L.,Moeller, N.H.,Banerjee, S.,Ferguson, L.,Kovaleva, M.,Porter, A.J.,Aihara, H.,LeBeau, A.M.,Barelle, C.J.
Mechanisms of SARS-CoV-2 neutralization by shark variable new antigen receptors elucidated through X-ray crystallography.
Nat Commun, 12:7325-7325, 2021

PubMed Abstract: Single-domain Variable New Antigen Receptors (VNARs) from the immune system of sharks are the smallest naturally occurring binding domains found in nature. Possessing flexible paratopes that can recognize protein motifs inaccessible to classical antibodies, VNARs have yet to be exploited for the development of SARS-CoV-2 therapeutics. Here, we detail the identification of a series of VNARs from a VNAR phage display library screened against the SARS-CoV-2 receptor binding domain (RBD). The ability of the VNARs to neutralize pseudotype and authentic live SARS-CoV-2 virus rivalled or exceeded that of full-length immunoglobulins and other single-domain antibodies. Crystallographic analysis of two VNARs found that they recognized separate epitopes on the RBD and had distinctly different mechanisms of virus neutralization unique to VNARs. Structural and biochemical data suggest that VNARs would be effective therapeutic agents against emerging SARS-CoV-2 mutants, including the Delta variant, and coronaviruses across multiple phylogenetic lineages. This study highlights the utility of VNARs as effective therapeutics against coronaviruses and may serve as a critical milestone for nearing a paradigm shift of the greater biologic landscape.

PubMed: 34916516
DOI: 10.1038/s41467-021-27611-y

Experimental method

X-RAY DIFFRACTION (1.92 Å)