7RQ6

Cryo-EM structure of SARS-CoV-2 spike in complex with non-neutralizing NTD-directed CV3-13 Fab isolated from convalescent individual

Summary for 7RQ6

• Entry DOI: 10.2210/pdb7rq6/pdb
• EMDB information: 24628
• Descriptor: Spike glycoprotein, CV3-13 Fab heavy chain, CV3-13 Fab light chain, ... (5 entities in total)
• Functional Keywords: human non-neutralizing mab, ntd-directed antibody, adcc, novel ntd epitope, sars-cov-2, spike, n-terminal domain, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 9
• Total formula weight: 565520.07

Authors

Chen, Y.,Pozharski, E.,Tolbert, W.D.,Pazgier, M. (deposition date: 2021-08-05, release date: 2022-04-20, Last modification date: 2024-11-13)

Primary citation

Beaudoin-Bussieres, G.,Chen, Y.,Ullah, I.,Prevost, J.,Tolbert, W.D.,Symmes, K.,Ding, S.,Benlarbi, M.,Gong, S.Y.,Tauzin, A.,Gasser, R.,Chatterjee, D.,Vezina, D.,Goyette, G.,Richard, J.,Zhou, F.,Stamatatos, L.,McGuire, A.T.,Charest, H.,Roger, M.,Pozharski, E.,Kumar, P.,Mothes, W.,Uchil, P.D.,Pazgier, M.,Finzi, A.
A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection.
Cell Rep, 38:110368-110368, 2022

PubMed Abstract: Emerging evidence indicates that both neutralizing and Fc-mediated effector functions of antibodies contribute to protection against SARS-CoV-2. It is unclear whether Fc-effector functions alone can protect against SARS-CoV-2. Here, we isolated CV3-13, a non-neutralizing antibody, from a convalescent individual with potent Fc-mediated effector functions. The cryoelectron microscopy structure of CV3-13 in complex with the SARS-CoV-2 spike reveals that the antibody binds from a distinct angle of approach to an N-terminal domain (NTD) epitope that only partially overlaps with the NTD supersite recognized by neutralizing antibodies. CV3-13 does not alter the replication dynamics of SARS-CoV-2 in K18-hACE2 mice, but its Fc-enhanced version significantly delays virus spread, neuroinvasion, and death in prophylactic settings. Interestingly, the combination of Fc-enhanced non-neutralizing CV3-13 with Fc-compromised neutralizing CV3-25 completely protects mice from lethal SARS-CoV-2 infection. Altogether, our data demonstrate that efficient Fc-mediated effector functions can potently contribute to the in vivo efficacy of anti-SARS-CoV-2 antibodies.

PubMed: 35123652
DOI: 10.1016/j.celrep.2022.110368

Experimental method

ELECTRON MICROSCOPY (4.18 Å)