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Subtle Influence of ACE2 Glycan Processing on SARS-CoV-2 Recognition.

Authors
  • Allen, Joel D1
  • Watanabe, Yasunori2
  • Chawla, Himanshi1
  • Newby, Maddy L1
  • Crispin, Max3
  • 1 School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
  • 2 School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Division of Structural Biology, University of Oxford, Wellcome Centre for Human Genetics, Oxford OX3 7BN, UK.
  • 3 School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK. Electronic address: [email protected]
Type
Published Article
Journal
Journal of Molecular Biology
Publisher
Elsevier
Publication Date
Feb 19, 2021
Volume
433
Issue
4
Pages
166762–166762
Identifiers
DOI: 10.1016/j.jmb.2020.166762
PMID: 33340519
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The severity of SARS-CoV-2 infection is highly variable and yet the molecular basis for this effect remains elusive. One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans. The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated. We therefore sought to investigate whether the glycosylation state of ACE2 impacts the interaction with SARS-CoV-2 viral spike. We generated a panel of engineered ACE2 glycoforms which were analyzed by mass spectrometry to reveal the site-specific glycan modifications. We then probed the impact of ACE2 glycosylation on S binding and revealed a subtle sensitivity with hypersialylated or oligomannose-type glycans slightly impeding the interaction. In contrast, deglycosylation of ACE2 did not influence SARS-CoV-2 binding. Overall, ACE2 glycosylation does not significantly influence viral spike binding. We suggest that any role of glycosylation in the pathobiology of SARS-CoV-2 will lie beyond its immediate impact of receptor glycosylation on virus binding. Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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