Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor
- PMID: 32841605
- PMCID: PMC7443692
- DOI: 10.1016/j.chom.2020.08.004
Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor
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.
Keywords: 3D modeling; ACE2; COVID-19; SARS-CoV-2; Spike protein; coronavirus; glycoprotein; glycosylation; mass spectrometry; molecular dynamics.
Copyright © 2020 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of Interests The authors declare no competing interests.
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Update of
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Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor.bioRxiv [Preprint]. 2020 Jul 24:2020.06.25.172403. doi: 10.1101/2020.06.25.172403. bioRxiv. 2020. Update in: Cell Host Microbe. 2020 Oct 7;28(4):586-601.e6. doi: 10.1016/j.chom.2020.08.004. PMID: 32743578 Free PMC article. Updated. Preprint.
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