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10.1016/j.antiviral.2020.104873

http://scihub22266oqcxt.onion/10.1016/j.antiviral.2020.104873
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suck abstract from ncbi


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pmid32653452      Antiviral+Res 2020 ; 181 (ä): 104873
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  • Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions #MMPMID32653452
  • Kim SY; Jin W; Sood A; Montgomery DW; Grant OC; Fuster MM; Fu L; Dordick JS; Woods RJ; Zhang F; Linhardt RJ
  • Antiviral Res 2020[Sep]; 181 (ä): 104873 PMID32653452show ga
  • Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread around the globe at an unprecedented rate. To date, no effective therapeutic is available to fight its associated disease, COVID-19. Our discovery of a novel insertion of glycosaminoglycan (GAG)-binding motif at S1/S2 proteolytic cleavage site (681-686 (PRRARS)) and two other GAG-binding-like motifs within SARS-CoV-2 spike glycoprotein (SGP) led us to hypothesize that host cell surface GAGs may interact SARS-CoV-2 SGPs to facilitate host cell entry. Using a surface plasmon resonance direct binding assay, we found that both monomeric and trimeric SARS-CoV-2 SGP bind more tightly to immobilized heparin (K(D) = 40 pM and 73 pM, respectively) than the SARS-CoV and MERS-CoV SGPs (500 nM and 1 nM, respectively). In competitive binding studies, the IC(50) of heparin, tri-sulfated non-anticoagulant heparan sulfate, and non-anticoagulant low molecular weight heparin against SARS-CoV-2 SGP binding to immobilized heparin were 0.056 muM, 0.12 muM, and 26.4 muM, respectively. Finally, unbiased computational ligand docking indicates that heparan sulfate interacts with the GAG-binding motif at the S1/S2 site on each monomer interface in the trimeric SARS-CoV-2 SGP, and at another site (453-459 (YRLFRKS)) when the receptor-binding domain is in an open conformation. The current study serves a foundation to further investigate biological roles of GAGs in SARS-CoV-2 pathogenesis. Furthermore, our findings may provide additional basis for further heparin-based interventions for COVID-19 patients exhibiting thrombotic complications.
  • |*Pandemics[MESH]
  • |Betacoronavirus/*metabolism[MESH]
  • |Binding Sites[MESH]
  • |COVID-19[MESH]
  • |Coronavirus Infections/*virology[MESH]
  • |Heparin/*metabolism[MESH]
  • |Humans[MESH]
  • |Kinetics[MESH]
  • |Molecular Docking Simulation[MESH]
  • |Pneumonia, Viral/*virology[MESH]
  • |Protein Binding[MESH]
  • |SARS-CoV-2[MESH]
  • |Severe Acute Respiratory Syndrome/*virology[MESH]
  • |Spike Glycoprotein, Coronavirus/*metabolism[MESH]


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