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10.1002/anie.202102717

http://scihub22266oqcxt.onion/10.1002/anie.202102717
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33860605!8250366!33860605
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suck abstract from ncbi


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pmid33860605      Angew+Chem+Int+Ed+Engl 2021 ; 60 (29): 15870-15878
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  • Polysulfates Block SARS-CoV-2 Uptake through Electrostatic Interactions* #MMPMID33860605
  • Nie C; Pouyan P; Lauster D; Trimpert J; Kerkhoff Y; Szekeres GP; Wallert M; Block S; Sahoo AK; Dernedde J; Pagel K; Kaufer BB; Netz RR; Ballauff M; Haag R
  • Angew Chem Int Ed Engl 2021[Jul]; 60 (29): 15870-15878 PMID33860605show ga
  • Here we report that negatively charged polysulfates can bind to the spike protein of SARS-CoV-2 via electrostatic interactions. Using a plaque reduction assay, we compare inhibition of SARS-CoV-2 by heparin, pentosan sulfate, linear polyglycerol sulfate (LPGS) and hyperbranched polyglycerol sulfate (HPGS). Highly sulfated LPGS is the optimal inhibitor, with an IC(50) of 67 mug mL(-1) (approx. 1.6 mum). This synthetic polysulfate exhibits more than 60-fold higher virus inhibitory activity than heparin (IC(50) : 4084 mug mL(-1) ), along with much lower anticoagulant activity. Furthermore, in molecular dynamics simulations, we verified that LPGS can bind more strongly to the spike protein than heparin, and that LPGS can interact even more with the spike protein of the new N501Y and E484K variants. Our study demonstrates that the entry of SARS-CoV-2 into host cells can be blocked via electrostatic interactions, therefore LPGS can serve as a blueprint for the design of novel viral inhibitors of SARS-CoV-2.
  • |A549 Cells[MESH]
  • |Animals[MESH]
  • |Antiviral Agents/chemistry/*metabolism[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Heparin/chemistry/*metabolism[MESH]
  • |Humans[MESH]
  • |Molecular Dynamics Simulation[MESH]
  • |Pentosan Sulfuric Polyester/chemistry/*metabolism[MESH]
  • |Polymers/chemistry/metabolism[MESH]
  • |Protein Binding[MESH]
  • |SARS-CoV-2/*chemistry[MESH]
  • |Spike Glycoprotein, Coronavirus/chemistry/*metabolism[MESH]
  • |Static Electricity[MESH]
  • |Vero Cells[MESH]


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