6WAQ

Crystal structure of the SARS-CoV-1 RBD bound by the cross-reactive single-domain antibody SARS VHH-72

Summary for 6WAQ

• Entry DOI: 10.2210/pdb6waq/pdb
• Descriptor: nanobody SARS VHH-72, Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: sars-cov-1, vhh, nanobody, rbd, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Lama glama; More
• Total number of polymer chains: 4
• Total formula weight: 71680.57

Authors

Wrapp, D.,McLellan, J.S. (deposition date: 2020-03-25, release date: 2020-04-01, Last modification date: 2024-10-16)

Primary citation

Wrapp, D.,De Vlieger, D.,Corbett, K.S.,Torres, G.M.,Wang, N.,Van Breedam, W.,Roose, K.,van Schie, L.,Hoffmann, M.,Pohlmann, S.,Graham, B.S.,Callewaert, N.,Schepens, B.,Saelens, X.,McLellan, J.S.
Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies.
Cell, 181:1004-, 2020

PubMed Abstract: Coronaviruses make use of a large envelope protein called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins play, they represent a vulnerable target for the development of therapeutics. Here, we describe the isolation of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs neutralize MERS-CoV or SARS-CoV-1 S pseudotyped viruses, respectively. Crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs interfere with receptor binding. We also show cross-reactivity between the SARS-CoV-1 S-directed VHH and SARS-CoV-2 S and demonstrate that this cross-reactive VHH neutralizes SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc-fusion. These data provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronavirus outbreaks.

PubMed: 32375025
DOI: 10.1016/j.cell.2020.04.031

Experimental method

X-RAY DIFFRACTION (2.2 Å)