Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2.
Science
; 369(6508): 1261-1265, 2020 09 04.
Article
in English
| MEDLINE | ID: covidwho-697063
ABSTRACT
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds angiotensin-converting enzyme 2 (ACE2) on host cells to initiate entry, and soluble ACE2 is a therapeutic candidate that neutralizes infection by acting as a decoy. By using deep mutagenesis, mutations in ACE2 that increase S binding are found across the interaction surface, in the asparagine 90-glycosylation motif and at buried sites. The mutational landscape provides a blueprint for understanding the specificity of the interaction between ACE2 and S and for engineering high-affinity decoy receptors. Combining mutations gives ACE2 variants with affinities that rival those of monoclonal antibodies. A stable dimeric variant shows potent SARS-CoV-2 and -1 neutralization in vitro. The engineered receptor is catalytically active, and its close similarity with the native receptor may limit the potential for viral escape.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Receptors, Virus
/
Protein Engineering
/
Peptidyl-Dipeptidase A
/
Spike Glycoprotein, Coronavirus
/
Betacoronavirus
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Science
Year:
2020
Document Type:
Article
Affiliation country:
Science.abc0870
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