Structural insights into the cross-neutralization of SARS-CoV and SARS-CoV-2 by the human monoclonal antibody 47D11.
Juliette FedryDaniel L HurdissChunyan WangWentao LiGonzalo ObalIeva DrulyteWenjuan DuStuart C HowesFrank J M van KuppeveldFriedrich G FörsterBerend-Jan BoschPublished in: Science advances (2021)
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.
Keyphrases
- sars cov
- monoclonal antibody
- respiratory syndrome coronavirus
- endothelial cells
- minimally invasive
- coronavirus disease
- binding protein
- small molecule
- cancer therapy
- transcription factor
- angiotensin ii
- dna methylation
- induced pluripotent stem cells
- ionic liquid
- dna binding
- pluripotent stem cells
- angiotensin converting enzyme