Protein glycosylation is essential for SARS-CoV-2 infection
Protein glycosylation is essential for SARS-CoV-2 infection
Abstract SARS-CoV-2 extensively N-glycosylates its surface spike (S) proteins. This post-translational modification is essential to modulate protein conformation and host cell invasion. Each S monomer can be modified with up to 22 N-glycans. To meet the high demand of protein glycosylation during virus replication, SARS-CoV-2 upregulates the expression of host N-glycosylation genes. Although a substantial amount of detail is known about the structure of S protein N-glycans, the role of N-glycosylation in SARS-CoV-2 infection remains largely undetermined. Here, we investigated the essentiality of the host N-glycosylation pathway and viral N-glycans for SARS-CoV-2 infection. When either monkey or human cells were preincubated with glycosylation inhibitors, including FDA-approved iminosugars, virus infection was significantly reduced. This infection phenotype was confirmed after RNAi knockdown of several glycosylation genes. In addition, enzymatic deglycosylation of whole viral particles confirmed that accessible oligosaccharides on the SARS-CoV-2 surface are essential for host cell infection. Altogether, we show evidence that the normal functioning of the host N- glycosylation machinery is essential not only for SARS-CoV-2 to infect, but also to produce new functional virions. These findings open the door for developing new approaches targeting N-glycosylation against COVID-19.
Patterson Edward I、Hughes Grant L、Acosta-Serrano ¨￠lvaro、Casas-Sanchez Aitor、Zech Tobias、Hargreaves Eleanor、Romero-Ramirez Alessandra
Department of Vector Biology and Liverpool School of Tropical Medicine||Department of Tropical Disease Biology, Liverpool School of Tropical MedicineDepartment of Vector Biology and Liverpool School of Tropical Medicine||Department of Tropical Disease Biology, Liverpool School of Tropical MedicineDepartment of Vector Biology and Liverpool School of Tropical Medicine||Department of Tropical Disease Biology, Liverpool School of Tropical MedicineDepartment of Vector Biology and Liverpool School of Tropical Medicine||Department of Tropical Disease Biology, Liverpool School of Tropical MedicineDepartment of Molecular and Cellular Physiology, University of LiverpoolDepartment of Molecular and Cellular Physiology, University of LiverpoolDepartment of Vector Biology and Liverpool School of Tropical Medicine||Department of Tropical Disease Biology, Liverpool School of Tropical Medicine
基础医学生物化学分子生物学
SARS-CoV-2COVID-19coronavirusN-glycosylationN-glycanviral infection
Patterson Edward I,Hughes Grant L,Acosta-Serrano ¨￠lvaro,Casas-Sanchez Aitor,Zech Tobias,Hargreaves Eleanor,Romero-Ramirez Alessandra.Protein glycosylation is essential for SARS-CoV-2 infection[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.02.05.429940.点此复制
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