7TCQ

Crystal structure of SARS-CoV-2 neutralizing antibody WS6 in complex with spike S2 peptide

Summary for 7TCQ

• Entry DOI: 10.2210/pdb7tcq/pdb
• Descriptor: Anti-SARS-CoV-2 antibody WS6 Fab heavy chain, Anti-SARS-CoV-2 antibody WS6 Fab light chain, Pegylated spike S2 peptide, ... (7 entities in total)
• Functional Keywords: sars-cov-2, spike, antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 6
• Total formula weight: 97942.59

Authors

Zhou, T.,Kwong, P.D. (deposition date: 2021-12-28, release date: 2022-08-03, Last modification date: 2024-11-13)

Primary citation

Shi, W.,Wang, L.,Zhou, T.,Sastry, M.,Yang, E.S.,Zhang, Y.,Chen, M.,Chen, X.,Choe, M.,Creanga, A.,Leung, K.,Olia, A.S.,Pegu, A.,Rawi, R.,Schon, A.,Shen, C.H.,Stancofski, E.D.,Talana, C.A.,Teng, I.T.,Wang, S.,Corbett, K.S.,Tsybovsky, Y.,Mascola, J.R.,Kwong, P.D.
Vaccine-elicited murine antibody WS6 neutralizes diverse beta-coronaviruses by recognizing a helical stem supersite of vulnerability.
Structure, 30:1233-, 2022

PubMed Abstract: Immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike elicits diverse antibodies, but it is unclear if any of the antibodies can neutralize broadly against other beta-coronaviruses. Here, we report antibody WS6 from a mouse immunized with mRNA encoding the SARS-CoV-2 spike. WS6 bound diverse beta-coronavirus spikes and neutralized SARS-CoV-2 variants, SARS-CoV, and related sarbecoviruses. Epitope mapping revealed WS6 to target a region in the S2 subunit, which was conserved among SARS-CoV-2, Middle East respiratory syndrome (MERS)-CoV, and hCoV-OC43. The crystal structure at 2 Å resolution of WS6 revealed recognition to center on a conserved S2 helix, which was occluded in both pre- and post-fusion spike conformations. Structural and neutralization analyses indicated WS6 to neutralize by inhibiting fusion and post-viral attachment. Comparison of WS6 with other recently identified antibodies that broadly neutralize beta-coronaviruses indicated a stem-helical supersite-centered on hydrophobic residues Phe1148, Leu1152, Tyr1155, and Phe1156-to be a promising target for vaccine design.

PubMed: 35841885
DOI: 10.1016/j.str.2022.06.004

Experimental method

X-RAY DIFFRACTION (2.02 Å)