8XK2

A neutralizing nanobody VHH60 against wt SARS-CoV-2

Summary for 8XK2

• Entry DOI: 10.2210/pdb8xk2/pdb
• Descriptor: Spike protein S1, VHH60 nanobody (2 entities in total)
• Functional Keywords: covid-19, spike glycoprotein, virus, antibody, viral protein/immune system, viral protein-immune system complex, antiviral protein, antiviral protein-immune system complex, antiviral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 8
• Total formula weight: 152402.68

Authors

Lu, Y.,Guo, H.,Ji, X.,Yang, H. (deposition date: 2023-12-22, release date: 2024-07-10, Last modification date: 2024-11-06)

Primary citation

Liu, Q.,Lu, Y.,Cai, C.,Huang, Y.,Zhou, L.,Guan, Y.,Fu, S.,Lin, Y.,Yan, H.,Zhang, Z.,Li, X.,Yang, X.,Yang, H.,Guo, H.,Lan, K.,Chen, Y.,Hou, S.C.,Xiong, Y.
A broad neutralizing nanobody against SARS-CoV-2 engineered from an approved drug.
Cell Death Dis, 15:458-458, 2024

PubMed Abstract: SARS-CoV-2 infection is initiated by Spike glycoprotein binding to the human angiotensin-converting enzyme 2 (ACE2) receptor via its receptor binding domain. Blocking this interaction has been proven to be an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody named VHH60, which was directly produced from an engineering nanobody library based on a commercialized nanobody within a very short period. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein at S, Sand S as determined by structural analysis, with an affinity of 2.56 nM. It inhibits infections of both ancestral SARS-CoV-2 strain and pseudotyped viruses harboring SARS-CoV-2 wildtype, key mutations or variants at the nanomolar level. Furthermore, VHH60 suppressed SARS-CoV-2 infection and propagation 50-fold better and protected mice from death for twice as long as the control group after SARS-CoV-2 nasal infections in vivo. Therefore, VHH60 is not only a powerful nanobody with a promising profile for disease control but also provides evidence for a highly effective and rapid approach to generating therapeutic nanobodies.

PubMed: 38937437
DOI: 10.1038/s41419-024-06802-7

Experimental method

X-RAY DIFFRACTION (3.4 Å)