7TPR

Camel nanobodies 7A3 and 8A2 broadly neutralize SARS-CoV-2 variants

Summary for 7TPR

• Entry DOI: 10.2210/pdb7tpr/pdb
• EMDB information: 26062
• Descriptor: Spike glycoprotein, Nanobody 8A2, Nanobody 7A3 (3 entities in total)
• Functional Keywords: neutralization, nanobody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 8
• Total formula weight: 449716.61

Authors

Butay, K.J.,Zhu, J.,Dandey, V.P.,Hong, J.,Kwon, H.J.,Chen, C.Z.,Duan, Z.,Li, D.,Ren, H.,Liang, T.,Martin, N.,Esposito, D.,Ortega-Rodriguez, U.,Xu, M.,Xie, H.,Ho, M.,Cachau, R.,Borgnia, M.J. (deposition date: 2022-01-25, release date: 2022-04-20, Last modification date: 2025-05-28)

Primary citation

Hong, J.,Kwon, H.J.,Cachau, R.,Chen, C.Z.,Dandey, V.P.,Martin, N.,Esposito, D.,Ortega-Rodriguez, U.,Xu, M.,Borgnia, M.J.,Xie, H.,Ho, M.
Camel nanobodies broadly neutralize SARS-CoV-2 variants
bioRxiv, 2021

PubMed Abstract: With the emergence of SARS-CoV-2 variants, there is urgent need to develop broadly neutralizing antibodies. Here, we isolate two V H nanobodies (7A3 and 8A2) from dromedary camels by phage display, which have high affinity for the receptor-binding domain (RBD) and broad neutralization activities against SARS-CoV-2 and its emerging variants. Cryo-EM complex structures reveal that 8A2 binds the RBD in its up mode and 7A3 inhibits receptor binding by uniquely targeting a highly conserved and deeply buried site in the spike regardless of the RBD conformational state. 7A3 at a dose of ≥5 mg/kg efficiently protects K18-hACE2 transgenic mice from the lethal challenge of B.1.351 or B.1.617.2, suggesting that the nanobody has promising therapeutic potentials to curb the COVID-19 surge with emerging SARS-CoV-2 variants.

PubMed: 34751270
DOI: 10.1101/2021.10.27.465996

Experimental method

ELECTRON MICROSCOPY (2.39 Å)