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Subtle influence of ACE2 glycan processing on SARS-CoV-2 recognition

Subtle influence of ACE2 glycan processing on SARS-CoV-2 recognition
Subtle influence of ACE2 glycan processing on SARS-CoV-2 recognition

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.

0022-2836
Allen, Joel D
c873d886-2a66-475b-ae04-57a10b37e716
Watanabe, Yasunori
8c0ee4af-a293-4de5-9036-3ce2051b380c
Chawla, Himanshi
07b9e983-4c35-4314-999d-fe3222a6c03b
Newby, Maddy L
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Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Allen, Joel D
c873d886-2a66-475b-ae04-57a10b37e716
Watanabe, Yasunori
8c0ee4af-a293-4de5-9036-3ce2051b380c
Chawla, Himanshi
07b9e983-4c35-4314-999d-fe3222a6c03b
Newby, Maddy L
417cba47-6a6f-42b9-8b9c-640f0518c621
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9

Allen, Joel D, Watanabe, Yasunori, Chawla, Himanshi, Newby, Maddy L and Crispin, Max (2020) Subtle influence of ACE2 glycan processing on SARS-CoV-2 recognition. Journal of Molecular Biology, 433 (4), [166762]. (doi:10.1016/j.jmb.2020.166762).

Record type: Article

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.

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Accepted/In Press date: 11 November 2020
e-pub ahead of print date: 17 December 2020

Identifiers

Local EPrints ID: 446910
URI: http://eprints.soton.ac.uk/id/eprint/446910
ISSN: 0022-2836
PURE UUID: ca00b5d8-42b2-4715-8ce7-269f67aa1eb6
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

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Date deposited: 26 Feb 2021 17:30
Last modified: 27 Feb 2021 02:50

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Contributors

Author: Joel D Allen
Author: Yasunori Watanabe
Author: Himanshi Chawla
Author: Maddy L Newby
Author: Max Crispin ORCID iD

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