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

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...

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Bibliographic Details
Published in:bioRxiv 2021-06
Main Authors: Casas-Sanchez, Aitor, Romero-Ramirez, Alessandra, Hargreaves, Eleanor, Ellis, Cameron C, Grajeda, Brian I, Estevao, Igor, Patterson, Edward I, Hughes, Grant L, Almeida, Igor C, Zech, Tobias, Acosta-Serrano, Alvaro
Format: Article
Language:English
Subjects:
COVID-19
Deglycosylation
Glycosylation
Immunotherapy
Infections
N-glycans
Oligosaccharides
Phenotypes
Polysaccharides
Post-translation
Protein structure
Proteins
RNA-mediated interference
Severe acute respiratory syndrome coronavirus 2
Virions
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Summary: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
DOI:10.1101/2021.02.05.429940