Structural insights into the cross-neutralization of SARS-CoV and SARS-CoV-2 by the human monoclonal antibody 47D11.
Sci Adv
; 7(23)2021 06.
Article
in English
| MEDLINE | ID: covidwho-1219234
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Severe acute respiratory syndrome-related coronavirus
/
Antibodies, Neutralizing
/
SARS-CoV-2
/
Antibodies, Monoclonal
/
Antibodies, Viral
Type of study:
Randomized controlled trials
Limits:
Humans
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Sciadv.abf5632
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