Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor.

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 r

SUBMITTER: Capraz T 

PROVIDER: S-EPMC8730730 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature