7X2L

Crystal structure of nanobody 3-2A2-4 with SARS-CoV-2 RBD

Summary for 7X2L

• Entry DOI: 10.2210/pdb7x2l/pdb
• Descriptor: Spike protein S1, Nanobody 3-2A2-4, beta-D-mannopyranose-(1-4)-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, nanobody, spike, receptor binding domain, 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: 2
• Total formula weight: 36209.32

Authors

Wang, X.Q.,Zhang, L.Q.,Ren, Y.F.,Li, M.X. (deposition date: 2022-02-25, release date: 2022-12-07, Last modification date: 2024-10-16)

Primary citation

Li, M.,Ren, Y.,Aw, Z.Q.,Chen, B.,Yang, Z.,Lei, Y.,Cheng, L.,Liang, Q.,Hong, J.,Yang, Y.,Chen, J.,Wong, Y.H.,Wei, J.,Shan, S.,Zhang, S.,Ge, J.,Wang, R.,Dong, J.Z.,Chen, Y.,Shi, X.,Zhang, Q.,Zhang, Z.,Chu, J.J.H.,Wang, X.,Zhang, L.
Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses.
Nat Commun, 13:7957-7957, 2022

PubMed Abstract: As SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we report on the identification of a special group of nanobodies from immunized alpaca with potency against diverse VOCs including Omicron subvariants BA.1, BA.2 and BA.4/5, SARS-CoV-1, and major sarbecoviruses. Crystal structure analysis of one representative nanobody, 3-2A2-4, discovers a highly conserved epitope located between the cryptic and the outer face of the receptor binding domain (RBD), distinctive from the receptor ACE2 binding site. Cryo-EM and biochemical evaluation reveal that 3-2A2-4 interferes structural alteration of RBD required for ACE2 binding. Passive delivery of 3-2A2-4 protects K18-hACE2 mice from infection of authentic SARS-CoV-2 Delta and Omicron. Identification of these unique nanobodies will inform the development of next generation antibody therapies and design of pan-sarbecovirus vaccines.

PubMed: 36575191
DOI: 10.1038/s41467-022-35642-2

Experimental method

X-RAY DIFFRACTION (2.4 Å)