Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry.
Angiotensin-Converting Enzyme 2
/ chemistry
Animals
Antibodies, Monoclonal
/ chemistry
Antibodies, Viral
/ chemistry
Antibody Affinity
Betacoronavirus
/ immunology
Broadly Neutralizing Antibodies
/ chemistry
COVID-19
/ immunology
Cross Reactions
Cryoelectron Microscopy
Epitopes
Humans
Immune Evasion
Mesocricetus
Models, Molecular
Molecular Mimicry
Mutation
Protein Conformation
Protein Domains
Receptors, Coronavirus
/ chemistry
SARS-CoV-2
/ immunology
Spike Glycoprotein, Coronavirus
/ chemistry
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
28 Jan 2022
28 Jan 2022
Historique:
pubmed:
7
1
2022
medline:
12
2
2022
entrez:
6
1
2022
Statut:
ppublish
Résumé
Understanding broadly neutralizing sarbecovirus antibody responses is key to developing countermeasures against SARS-CoV-2 variants and future zoonotic sarbecoviruses. We describe the isolation and characterization of a human monoclonal antibody, designated S2K146, that broadly neutralizes viruses belonging to SARS-CoV- and SARS-CoV-2-related sarbecovirus clades which use ACE2 as an entry receptor. Structural and functional studies show that most of the virus residues that directly bind S2K146 are also involved in binding to ACE2. This allows the antibody to potently inhibit receptor attachment. S2K146 protects against SARS-CoV-2 Beta challenge in hamsters and viral passaging experiments reveal a high barrier for emergence of escape mutants, making it a good candidate for clinical development. The conserved ACE2-binding residues present a site of vulnerability that might be leveraged for developing vaccines eliciting broad sarbecovirus immunity.
Identifiants
pubmed: 34990214
doi: 10.1126/science.abm8143
pmc: PMC9400459
mid: NIHMS1830835
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Viral
0
Broadly Neutralizing Antibodies
0
Epitopes
0
Receptors, Coronavirus
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
449-454Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM120553
Pays : United States
Organisme : NIAID NIH HHS
ID : DP1 AI158186
Pays : United States
Organisme : NIH HHS
ID : S10 OD023476
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008268
Pays : United States
Commentaires et corrections
Type : UpdateOf
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