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10.7554/eLife.61552

http://scihub22266oqcxt.onion/10.7554/eLife.61552
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33103998!7685702!33103998
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suck abstract from ncbi


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pmid33103998      Elife 2020 ; 9 (ä): ä
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  • Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration #MMPMID33103998
  • Yang Q; Hughes TA; Kelkar A; Yu X; Cheng K; Park S; Huang WC; Lovell JF; Neelamegham S
  • Elife 2020[Oct]; 9 (ä): ä PMID33103998show ga
  • The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated. The impact of this post-translational modification on viral entry is yet unestablished. We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus. We observed that N- and O-glycans had only minor contribution to Spike-ACE2 binding. However, these carbohydrates played a major role in regulating viral entry. Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells. Blocking O-glycan elaboration also partially blocked viral entry. Mechanistic studies suggest multiple roles for glycans during viral entry. Among them, inhibition of N-glycan biosynthesis enhanced Spike-protein proteolysis. This could reduce RBD presentation on virus, lowering binding to host ACE2 and decreasing viral entry. Overall, chemical inhibitors of glycosylation may be evaluated for COVID-19.
  • |Alkaloids/pharmacology[MESH]
  • |Angiotensin-Converting Enzyme 2/*chemistry/metabolism[MESH]
  • |Gene Knockout Techniques[MESH]
  • |Glycosylation/drug effects[MESH]
  • |HEK293 Cells[MESH]
  • |Host Microbial Interactions/drug effects[MESH]
  • |Humans[MESH]
  • |Mass Spectrometry[MESH]
  • |Molecular Dynamics Simulation[MESH]
  • |Polysaccharides/*biosynthesis/metabolism[MESH]
  • |Protein Binding[MESH]
  • |Protein Processing, Post-Translational/drug effects[MESH]
  • |Receptors, Virus/*chemistry/metabolism[MESH]
  • |SARS-CoV-2/drug effects/genetics/metabolism/*physiology[MESH]
  • |Spike Glycoprotein, Coronavirus/*chemistry/metabolism[MESH]


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