Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor.
Elife
; 102021 12 20.
Article
em En
| MEDLINE
| ID: mdl-34927585
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polissacarídeos
/
Receptores Virais
/
Simulação de Dinâmica Molecular
/
Glicoproteína da Espícula de Coronavírus
/
Enzima de Conversão de Angiotensina 2
/
SARS-CoV-2
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Elife
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Áustria