8TZU

OC43 S1b domain in complex with WNb 293 and WNb 317

Summary for 8TZU

• Entry DOI: 10.2210/pdb8tzu/pdb
• Descriptor: Spike protein S1, WNb 317, WNb 293, ... (8 entities in total)
• Functional Keywords: antibody, sars-cov-2 spike, complex, viral protein
• Biological source: Human coronavirus OC43; More
• Total number of polymer chains: 8
• Total formula weight: 160341.85

Authors

Pymm, P.,Feng, J.,Tham, W.H. (deposition date: 2023-08-27, release date: 2024-05-01, Last modification date: 2024-11-13)

Primary citation

Adair, A.,Tan, L.L.,Feng, J.,Girkin, J.,Bryant, N.,Wang, M.,Mordant, F.,Chan, L.-J.,Bartlett, N.W.,Subbarao, K.,Pymm, P.,Tham, W.-H.
Human coronavirus OC43 nanobody neutralizes virus and protects mice from infection.
J.Virol., 98:e0053124-e0053124, 2024

PubMed Abstract: Human coronavirus (hCoV) OC43 is endemic to global populations and usually causes asymptomatic or mild upper respiratory tract illness. Here, we demonstrate the neutralization efficacy of isolated nanobodies from alpacas immunized with the S1 and S1 domain of the hCoV-OC43 spike glycoprotein. A total of 40 nanobodies bound to recombinant OC43 protein with affinities ranging from 1 to 149 nM. Two nanobodies WNb 293 and WNb 294 neutralized virus at 0.21 and 1.79 nM, respectively. Intranasal and intraperitoneal delivery of WNb 293 fused to an Fc domain significantly reduced nasal viral load in a mouse model of hCoV-OC43 infection. Using X-ray crystallography, we observed that WNb 293 bound to an epitope on the OC43 S1B domain, distal from the sialoglycan-binding site involved in host cell entry. This result suggests that neutralization mechanism of this nanobody does not involve disruption of glycan binding. Our work provides characterization of nanobodies against hCoV-OC43 that blocks virus entry and reduces viral loads and may contribute to future nanobody-based therapies for hCoV-OC43 infections.

PubMed: 38709106
DOI: 10.1128/jvi.00531-24

Experimental method

X-RAY DIFFRACTION (2.9 Å)