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Protein N-glycosylation is essential for SARS-CoV-2 infection

View ORCID ProfileAitor Casas-Sanchez, Alessandra Romero-Ramirez, Eleanor Hargreaves, Cameron C. Ellis, Brian I. Grajeda, Igor Estevao, Edward I. Patterson, View ORCID ProfileGrant L. Hughes, View ORCID ProfileIgor C. Almeida, Tobias Zech, View ORCID ProfileÁlvaro Acosta-Serrano
doi: https://doi.org/10.1101/2021.02.05.429940
Aitor Casas-Sanchez
1Department of Vector Biology, Liverpool School of Tropical Medicine, UK
2Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, UK
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  • For correspondence: aitor.casas-sanchez@lstmed.ac.uk
Alessandra Romero-Ramirez
1Department of Vector Biology, Liverpool School of Tropical Medicine, UK
2Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, UK
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Eleanor Hargreaves
3Department of Molecular and Cellular Physiology, University of Liverpool, UK
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Cameron C. Ellis
4Department of Biological Sciences, Border Biomedical Research Center, University of Texas at El Paso, TX, USA
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Brian I. Grajeda
4Department of Biological Sciences, Border Biomedical Research Center, University of Texas at El Paso, TX, USA
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Igor Estevao
4Department of Biological Sciences, Border Biomedical Research Center, University of Texas at El Paso, TX, USA
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Edward I. Patterson
1Department of Vector Biology, Liverpool School of Tropical Medicine, UK
2Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, UK
5Department of Biological Sciences, Brock University, Canada
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Grant L. Hughes
1Department of Vector Biology, Liverpool School of Tropical Medicine, UK
2Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, UK
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Igor C. Almeida
4Department of Biological Sciences, Border Biomedical Research Center, University of Texas at El Paso, TX, USA
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Tobias Zech
3Department of Molecular and Cellular Physiology, University of Liverpool, UK
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Álvaro Acosta-Serrano
1Department of Vector Biology, Liverpool School of Tropical Medicine, UK
2Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, UK
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Abstract

SARS-CoV-2 extensively N-glycosylates its spike proteins, which are necessary for host cell invasion and the target of both vaccines and immunotherapies. These sugars are predicted to help mediate spike binding to the host receptor by stabilizing its ‘open’ conformation and evading host immunity. Here, we investigated both the essentiality of the host N-glycosylation pathway and SARS-CoV-2 N-glycans for infection. Inhibition of host N-glycosylation using RNAi or FDA-approved drugs reduced virus infectivity, including that of several variants. Under these conditions, cells produced less virions and some completely lost their infectivity. Furthermore, partial deglycosylation of intact virions showed that surface-exposed N-glycans are critical for cell invasion. Altogether, spike N-glycosylation is a targetable pathway with clinical potential for treatment or prevention of COVID-19.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Updated manuscript with significant changes

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 04, 2021.
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Protein N-glycosylation is essential for SARS-CoV-2 infection
Aitor Casas-Sanchez, Alessandra Romero-Ramirez, Eleanor Hargreaves, Cameron C. Ellis, Brian I. Grajeda, Igor Estevao, Edward I. Patterson, Grant L. Hughes, Igor C. Almeida, Tobias Zech, Álvaro Acosta-Serrano
bioRxiv 2021.02.05.429940; doi: https://doi.org/10.1101/2021.02.05.429940
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Protein N-glycosylation is essential for SARS-CoV-2 infection
Aitor Casas-Sanchez, Alessandra Romero-Ramirez, Eleanor Hargreaves, Cameron C. Ellis, Brian I. Grajeda, Igor Estevao, Edward I. Patterson, Grant L. Hughes, Igor C. Almeida, Tobias Zech, Álvaro Acosta-Serrano
bioRxiv 2021.02.05.429940; doi: https://doi.org/10.1101/2021.02.05.429940

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