7UL0

Crystal structure of SARS-CoV-2 RBD in complex with the ridge-binding nAb EH8 isolated from a nonvaccinated pediatric patient

Summary for 7UL0

• Entry DOI: 10.2210/pdb7ul0/pdb
• Descriptor: Spike protein S1, Heavy chain of EH8, Light chain of EH8, ... (7 entities in total)
• Functional Keywords: pediatric neutralizing mab, rbd-ridge-targeting, bind to both closed and open sars-cov-2 spike, class-2 rbd-binding antibody, 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: 3
• Total formula weight: 72263.48

Authors

Chen, Y.,Tolbert, W.D.,Bai, X.,Pazgier, M. (deposition date: 2022-04-03, release date: 2023-03-08, Last modification date: 2024-10-23)

Primary citation

Chen, Y.,Prevost, J.,Ullah, I.,Romero, H.,Lisi, V.,Tolbert, W.D.,Grover, J.R.,Ding, S.,Gong, S.Y.,Beaudoin-Bussieres, G.,Gasser, R.,Benlarbi, M.,Vezina, D.,Anand, S.P.,Chatterjee, D.,Goyette, G.,Grunst, M.W.,Yang, Z.,Bo, Y.,Zhou, F.,Beland, K.,Bai, X.,Zeher, A.R.,Huang, R.K.,Nguyen, D.N.,Sherburn, R.,Wu, D.,Piszczek, G.,Pare, B.,Matthies, D.,Xia, D.,Richard, J.,Kumar, P.,Mothes, W.,Cote, M.,Uchil, P.D.,Lavallee, V.P.,Smith, M.A.,Pazgier, M.,Haddad, E.,Finzi, A.
Molecular basis for antiviral activity of two pediatric neutralizing antibodies targeting SARS-CoV-2 Spike RBD.
Iscience, 26:105783-105783, 2023

PubMed Abstract: Neutralizing antibodies (NAbs) hold great promise for clinical interventions against SARS-CoV-2 variants of concern (VOCs). Understanding NAb epitope-dependent antiviral mechanisms is crucial for developing vaccines and therapeutics against VOCs. Here we characterized two potent NAbs, EH3 and EH8, isolated from an unvaccinated pediatric patient with exceptional plasma neutralization activity. EH3 and EH8 cross-neutralize the early VOCs and mediate strong Fc-dependent effector activity . Structural analyses of EH3 and EH8 in complex with the receptor-binding domain (RBD) revealed the molecular determinants of the epitope-driven protection and VOC evasion. While EH3 represents the prevalent IGHV3-53 NAb whose epitope substantially overlaps with the ACE2 binding site, EH8 recognizes a narrow epitope exposed in both RBD-up and RBD-down conformations. When tested a single-dose prophylactic administration of EH3 fully protected stringent K18-hACE2 mice from lethal challenge with Delta VOC. Our study demonstrates that protective NAbs responses converge in pediatric and adult SARS-CoV-2 patients.

PubMed: 36514310
DOI: 10.1016/j.isci.2022.105783

Experimental method

X-RAY DIFFRACTION (2.49 Å)