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http://purl.uniprot.org/citations/32653452http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/32653452http://www.w3.org/2000/01/rdf-schema#comment"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 (KD = 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 IC50 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 μM, 0.12 μM, and 26.4 μM, 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."xsd:string
http://purl.uniprot.org/citations/32653452http://purl.org/dc/terms/identifier"doi:10.1016/j.antiviral.2020.104873"xsd:string
http://purl.uniprot.org/citations/32653452http://purl.uniprot.org/core/author"Fu L."xsd:string
http://purl.uniprot.org/citations/32653452http://purl.uniprot.org/core/author"Jin W."xsd:string
http://purl.uniprot.org/citations/32653452http://purl.uniprot.org/core/author"Kim S.Y."xsd:string
http://purl.uniprot.org/citations/32653452http://purl.uniprot.org/core/author"Zhang F."xsd:string
http://purl.uniprot.org/citations/32653452http://purl.uniprot.org/core/author"Linhardt R.J."xsd:string
http://purl.uniprot.org/citations/32653452http://purl.uniprot.org/core/author"Dordick J.S."xsd:string
http://purl.uniprot.org/citations/32653452http://purl.uniprot.org/core/author"Sood A."xsd:string
http://purl.uniprot.org/citations/32653452http://purl.uniprot.org/core/author"Woods R.J."xsd:string
http://purl.uniprot.org/citations/32653452http://purl.uniprot.org/core/author"Grant O.C."xsd:string
http://purl.uniprot.org/citations/32653452http://purl.uniprot.org/core/author"Fuster M.M."xsd:string
http://purl.uniprot.org/citations/32653452http://purl.uniprot.org/core/author"Montgomery D.W."xsd:string
http://purl.uniprot.org/citations/32653452http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/32653452http://purl.uniprot.org/core/name"Antiviral Res"xsd:string
http://purl.uniprot.org/citations/32653452http://purl.uniprot.org/core/pages"104873"xsd:string
http://purl.uniprot.org/citations/32653452http://purl.uniprot.org/core/title"Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions."xsd:string
http://purl.uniprot.org/citations/32653452http://purl.uniprot.org/core/volume"181"xsd:string
http://purl.uniprot.org/citations/32653452http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/32653452
http://purl.uniprot.org/citations/32653452http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/32653452
http://purl.uniprot.org/uniprot/#_P34741-mappedCitation-32653452http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32653452
http://purl.uniprot.org/uniprot/#_P18827-mappedCitation-32653452http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32653452
http://purl.uniprot.org/uniprot/#_P51654-mappedCitation-32653452http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32653452
http://purl.uniprot.org/uniprot/#_O00468-mappedCitation-32653452http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32653452