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TitleStructural insights into the cross-neutralization of SARS-CoV and SARS-CoV-2 by the human monoclonal antibody 47D11.
Journal, issue, pagesSci Adv, Vol. 7, Issue 23, Year 2021
Publish dateJun 2, 2021
AuthorsJuliette Fedry / Daniel L Hurdiss / Chunyan Wang / Wentao Li / Gonzalo Obal / Ieva Drulyte / Wenjuan Du / Stuart C Howes / Frank J M van Kuppeveld / Friedrich Förster / Berend-Jan Bosch /
PubMed AbstractThe 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- ...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.
External linksSci Adv / PubMed:33958322 / PubMed Central
MethodsEM (single particle)
Resolution3.8 - 4.0 Å
Structure data

11812

7akd

EMDB-11812, PDB-7akd:
Structure of the SARS-CoV-2 spike glycoprotein in complex with the 47D11 neutralizing antibody Fab fragment
Method: EM (single particle) / Resolution: 4.0 Å

11813

7akj

EMDB-11813, PDB-7akj:
Structure of the SARS-CoV spike glycoprotein in complex with the 47D11 neutralizing antibody Fab fragment
Method: EM (single particle) / Resolution: 3.8 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-FUC:
alpha-L-fucopyranose / Fucose

ChemComp-MAN:
alpha-D-mannopyranose / Mannose

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
  • sars coronavirus wh20
KeywordsVIRAL PROTEIN / SARS-coV-2 / spike / neutralizing antibody / SARS-coV

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