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Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor. Cell Host Microbe 2020 Oct 07;28(4):586-601.e6

Date

08/26/2020

Pubmed ID

32841605

Pubmed Central ID

PMC7443692

DOI

10.1016/j.chom.2020.08.004

Scopus ID

2-s2.0-85090566044 (requires institutional sign-in at Scopus site)   345 Citations

Abstract

The SARS-CoV-2 betacoronavirus uses its highly glycosylated trimeric Spike protein to bind to the cell surface receptor angiotensin converting enzyme 2 (ACE2) glycoprotein and facilitate host cell entry. We utilized glycomics-informed glycoproteomics to characterize site-specific microheterogeneity of glycosylation for a recombinant trimer Spike mimetic immunogen and for a soluble version of human ACE2. We combined this information with bioinformatics analyses of natural variants and with existing 3D structures of both glycoproteins to generate molecular dynamics simulations of each glycoprotein both alone and interacting with one another. Our results highlight roles for glycans in sterically masking polypeptide epitopes and directly modulating Spike-ACE2 interactions. Furthermore, our results illustrate the impact of viral evolution and divergence on Spike glycosylation, as well as the influence of natural variants on ACE2 receptor glycosylation. Taken together, these data can facilitate immunogen design to achieve antibody neutralization and inform therapeutic strategies to inhibit viral infection.

Author List

Zhao P, Praissman JL, Grant OC, Cai Y, Xiao T, Rosenbalm KE, Aoki K, Kellman BP, Bridger R, Barouch DH, Brindley MA, Lewis NE, Tiemeyer M, Chen B, Woods RJ, Wells L

Author

Kazuhiro Aoki PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Betacoronavirus
Coronavirus Infections
Glycosylation
HEK293 Cells
Humans
Molecular Dynamics Simulation
Pandemics
Peptidyl-Dipeptidase A
Pneumonia, Viral
Protein Domains
Protein Interaction Domains and Motifs
Receptors, Virus
Spike Glycoprotein, Coronavirus
Virus Internalization