7W1S

Crystal structure of SARS-CoV-2 spike receptor-binding domain in complex with neutralizing nanobody Nb-007

Summary for 7W1S

• Entry DOI: 10.2210/pdb7w1s/pdb
• Descriptor: Spike protein S1, Nanobody Nb-007 (3 entities in total)
• Functional Keywords: viral protein/immune system, viral protein-immune system complex
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 2
• Total formula weight: 37621.24

Authors

Yang, J.,Lin, S.,Sun, H.L.,Lu, G.W. (deposition date: 2021-11-20, release date: 2022-06-29, Last modification date: 2024-10-16)

Primary citation

Yang, J.,Lin, S.,Sun, H.,Chen, Z.,Yang, F.,Lin, X.,Guo, L.,Wang, L.,Wen, A.,Zhang, X.,Dai, Y.,He, B.,Cao, Y.,Dong, H.,Liu, X.,Chen, B.,Li, J.,Zhao, Q.,Lu, G.
A Potent Neutralizing Nanobody Targeting the Spike Receptor-Binding Domain of SARS-CoV-2 and the Structural Basis of Its Intimate Binding.
Front Immunol, 13:820336-820336, 2022

PubMed Abstract: The continuous spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world has raised unprecedented challenges to the human society. Antibodies and nanobodies possessing neutralization activity represent promising drug candidates. In this study, we report the identification and characterization of a potent SARS-CoV-2 neutralizing nanobody that targets the viral spike receptor-binding domain (S-RBD). The nanobody, termed as Nb-007, engages SARS-CoV-2 S-RBD with the two-digit picomolar binding affinity and shows outstanding virus entry-inhibition activity. The complex structure of Nb-007 bound to SARS-CoV-2 S-RBD reveals an epitope that is partially overlapping with the binding site for the human receptor of angiotensin-converting enzyme 2 (ACE2). The nanobody therefore exerts neutralization by competing with ACE2 for S-RBD binding, which is further ascertained by our biochemical analyses. Finally, we also show that Nb-007 reserves promising, though compromised, neutralization activity against the currently-circulating Delta variant and that fusion of the nanobody with Fc dramatically increases its entry-inhibition capacity. Taken together, these data have paved the way of developing Nb-007 as a drug-reserve for potential treatment of SARS-CoV-2 related diseases.

PubMed: 35663966
DOI: 10.3389/fimmu.2022.820336

Experimental method

X-RAY DIFFRACTION (1.997 Å)