2021
DOI: 10.7554/elife.73641
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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. Engineeri… Show more

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Cited by 32 publications
(52 citation statements)
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“… 27 Both the spike protein and ACE2 also contain several glycans. 4 , 35 38 These glycans act as a shield to the host immune response. 39 41 Also, several studies have revealed that these glycans play important roles in developing favorable conformation of the receptor binding domain (RBD) for binding with ACE2.…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“… 27 Both the spike protein and ACE2 also contain several glycans. 4 , 35 38 These glycans act as a shield to the host immune response. 39 41 Also, several studies have revealed that these glycans play important roles in developing favorable conformation of the receptor binding domain (RBD) for binding with ACE2.…”
Section: Introductionmentioning
confidence: 99%
“… 39 41 Also, several studies have revealed that these glycans play important roles in developing favorable conformation of the receptor binding domain (RBD) for binding with ACE2. 35 , 39 …”
Section: Introductionmentioning
confidence: 99%
“…Mutations described for the Omicron VOC are depicted in red. Shown in yellow are the glycan modifications of the spike protein (Capraz et al , 2021 ). Table lists the SARS‐CoV‐2 strains and their respective mutations within the Spike protein that were used in this study.…”
Section: Resultsmentioning
confidence: 99%
“…Mutations described for the Omicron VOC are depicted in red. Shown in yellow are the glycan modifications of the spike protein (Capraz et al , 2021 ).…”
Section: Resultsmentioning
confidence: 99%
“…A structure-guided glyco-engineering approach has also received recognition for optimizing ACE2 for efficient virus inhibition. [131] In complementation with molecular dynamics (MD) simulations, the approach revealed some attractive N-glycan hotspots on ACE2 that improves binding affinity and neutralization competency of SARS-CoV-2 and associated viruses.…”
Section: Promising Bionanotechnology Approaches To Achieve Improved T...mentioning
confidence: 99%