Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor.
Elife
; 102021 12 20.
Article
in English
| MEDLINE | ID: covidwho-1592091
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
Infection and viral entry of SARS-CoV-2 crucially depends on the binding of its Spike protein to angiotensin converting enzyme 2 (ACE2) presented on host cells. Glycosylation of both proteins is critical for this interaction. Recombinant soluble human ACE2 can neutralize SARS-CoV-2 and is currently undergoing clinical tests for the treatment of COVID-19. We used 3D structural models and molecular dynamics simulations to define the ACE2 N-glycans that critically influence Spike-ACE2 complex formation. Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein. Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Polysaccharides
/
Receptors, Virus
/
Molecular Dynamics Simulation
/
Spike Glycoprotein, Coronavirus
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
ELife.73641
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