About: Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry

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About: Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry
Creator	Fu, Li Montgomery, David Kim, So Woods, Robert Dordick, Jonathan Fuster, Mark Grant, Oliver Jin, Weihua Linhardt, Robert Sood, Amika Zhang, Fuming
Source	BioRxiv
abstract	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 might be involved in host cell entry of SARS-CoV-2. Using a surface plasmon resonance direct binding assay, we found that both monomeric and trimeric SARS-CoV-2 spike more tightly bind 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. Our study augments our knowledge in SARS-CoV-2 pathogenesis and advances carbohydrate-based COVID-19 therapeutic development.
has issue date	2020-04-15(xsd:dateTime)
bibo:doi	10.1101/2020.04.14.041459
has license	biorxiv
sha1sum (hex)	203172447b1e6aac66c13dd8fe0d98ff5fbdb481
schema:url	https://doi.org/10.1101/2020.04.14.041459
resource representing a document's title	Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry
schema:publication	bioRxiv
resource representing a document's body	covid:203172447b1e6aac66c13dd8fe0d98ff5fbdb481#body_text
is schema:about of	named entity 'development' named entity 'monomer' named entity 'binding' named entity 'immobilized' named entity 'surface' named entity 'computational' named entity 'continues' named entity 'proteolytic cleavage' named entity 'coronavirus' named entity '686' named entity 'SARS-COV-2' named entity 'COMPETITIVE BINDING' named entity 'INVOLVED' named entity 'DISCOVERY' named entity 'CLEAVAGE' named entity 'LIGAND' named entity 'ENTRY' named entity 'GLYCOSAMINOGLYCAN' named entity 'LIKE' named entity 'NOVEL' named entity 'FOUND' named entity 'HEPARAN SULFATE' named entity 'SITE' named entity 'EFFECTIVE' named entity 'AVAILABLE' named entity 'TRI' named entity 'SARS-CoV-2' named entity 'therapeutic' named entity 'Severe acute respiratory syndrome-related coronavirus' named entity 'SARS-CoV-2' named entity 'trimeric' named entity 'motif' named entity 'augments' named entity 'surface plasmon' named entity 'SARS-CoV-2' named entity 'SARS-CoV-2' named entity 'SARS-CoV' named entity 'pathogenesis' named entity 'MERS-CoV' named entity 'anticoagulant' named entity 'motif' named entity 'heparin' named entity 'heparan sulfate' named entity 'SARS-CoV-2' named entity 'SARS-CoV-2' named entity 'anticoagulant' named entity 'Severe acute respiratory syndrome-related coronavirus' named entity 'therapeutic development' named entity 'cell entry' named entity 'discovery' named entity 'TMPRSS2' named entity 'host cell' named entity 'virions' named entity 'inter-domain' named entity 'GAGs' named entity 'protein' named entity 'SARS-CoV-2' named entity 'cell surface' named entity 'binding site' named entity 'SARS-CoV' named entity 'protease' named entity 'disaccharide' named entity 'MERS-CoV' named entity 'GAGs' named entity 'World Health Organization' named entity 'heparin' named entity 'GE Healthcare' named entity 'arginine' named entity 'ECM' named entity 'SARS-CoV' named entity 'reagent' named entity 'spike proteins' named entity 'motif' named entity 'sulfation'

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