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10.1007/s10875-020-00905-4

http://scihub22266oqcxt.onion/10.1007/s10875-020-00905-4
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33245474!7691692!33245474
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suck abstract from ncbi


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pmid33245474      J+Clin+Immunol 2021 ; 41 (2): 335-344
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  • N-Glycan Modification in Covid-19 Pathophysiology: In vitro Structural Changes with Limited Functional Effects #MMPMID33245474
  • Nunes-Santos CJ; Kuehn HS; Rosenzweig SD
  • J Clin Immunol 2021[Feb]; 41 (2): 335-344 PMID33245474show ga
  • In 2014, we reported two siblings with a rare congenital disorder of glycosylation due to mutations in mannosyl-oligosaccharide glucosidase (MOGS). The glycan alteration derived from this disease resulted in an in vitro infection resistance to particular enveloped, N-glycosylation-dependent viruses as influenza and HIV. As part of the global effort to find safe and effective antiviral therapies for Covid-19, we assessed the in vitro activity of the FDA-approved alpha-glucosidase inhibitor miglustat against SARS-CoV-2. Expression plasmids encoding SARS-CoV-2 spike (S) and human ACE2 glycoproteins (GP) were tested to evaluate N-glycan modifications induced by alpha-glucosidase inhibition. Immunoprecipitation was used to assess binding between these two GP. Cell-to-cell fusion was assessed by immunofluorescence of cocultures of SARS-CoV-2 S and ACE2-expressing cells. Miglustat effect on immune response was tested by measuring cytokine release from PBMC exposed to purified SARS-CoV-2 S. In our overexpression system, miglustat successfully and specifically modified N-glycans in both SARS-CoV-2 S and its main receptor ACE2. Binding between these two GP was not affected by glycan modifications. A surrogate marker for viral cytopathic effect, measured as receptor-dependent SARS-CoV-2 S-driven cell-to-cell fusion, was not disrupted by miglustat treatment. This observation was further confirmed in MOGS-null transfected cells. Miglustat produced no statistically significant effects on cytokine production following SARS-CoV-2 S glycoprotein stimulation of PBMC. Our work shows that despite clear N-glycan alteration in the presence of miglustat, the functions of the Covid-19-related glycoproteins studied were not affected, making it unlikely that miglustat can change the natural course of the disease.
  • |*Host-Pathogen Interactions[MESH]
  • |*SARS-CoV-2[MESH]
  • |Angiotensin-Converting Enzyme 2/genetics/metabolism[MESH]
  • |Animals[MESH]
  • |COVID-19/*metabolism/*virology[MESH]
  • |Cytokines/metabolism[MESH]
  • |Estrogen Receptor alpha/metabolism[MESH]
  • |Glycosylation[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |Mice[MESH]
  • |NIH 3T3 Cells[MESH]
  • |Peptidyl-Dipeptidase A/genetics/metabolism[MESH]


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