7AKD

Structure of the SARS-CoV-2 spike glycoprotein in complex with the 47D11 neutralizing antibody Fab fragment

Summary for 7AKD

• Entry DOI: 10.2210/pdb7akd/pdb
• EMDB information: 11812
• Descriptor: Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-L-fucopyranose, ... (12 entities in total)
• Functional Keywords: sars-cov-2, spike, neutralizing antibody, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 7
• Total formula weight: 490247.63

Authors

Fedry, J.,Hurdiss, D.L.,Wang, C.,Li, W.,Obal, G.,Drulyte, I.,Howes, S.C.,van Kuppeveld, F.J.M.,Foerster, F.,Bosch, B.J. (deposition date: 2020-09-30, release date: 2021-05-19, Last modification date: 2021-06-16)

Primary citation

Fedry, J.,Hurdiss, D.L.,Wang, C.,Li, W.,Obal, G.,Drulyte, I.,Du, W.,Howes, S.C.,van Kuppeveld, F.J.M.,Forster, F.,Bosch, B.J.
Structural insights into the cross-neutralization of SARS-CoV and SARS-CoV-2 by the human monoclonal antibody 47D11.
Sci Adv, 7:-, 2021

PubMed Abstract: The emergence of SARS-CoV-2 antibody escape mutations highlights the urgent need for broadly neutralizing therapeutics. We previously identified a human monoclonal antibody, 47D11, capable of cross-neutralizing SARS-CoV-2 and SARS-CoV and protecting against the associated respiratory disease in an animal model. Here, we report cryo-EM structures of both trimeric spike ectodomains in complex with the 47D11 Fab. 47D11 binds to the closed receptor-binding domain, distal to the ACE2 binding site. The CDRL3 stabilizes the N343 glycan in an upright conformation, exposing a mutationally constrained hydrophobic pocket, into which the CDRH3 loop inserts two aromatic residues. 47D11 stabilizes a partially open conformation of the SARS-CoV-2 spike, suggesting that it could be used effectively in combination with other antibodies targeting the exposed receptor-binding motif. Together, these results reveal a cross-protective epitope on the SARS-CoV-2 spike and provide a structural roadmap for the development of 47D11 as a prophylactic or postexposure therapy for COVID-19.

PubMed: 33958322
DOI: 10.1126/sciadv.abf5632

Experimental method

ELECTRON MICROSCOPY (4 Å)