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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/1970| Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry | |
| So Young Kim. Weihua Jin. Amika Sood. David W. Montgomery. Oliver C. Grant. Mark M. Fuster. Li Fu. Jonathan S. Dordick. Robert J. Woods. Fuming Zhang. Robert J. Linhardt. | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| 10.1101/2020.04.14.041459 | |
| 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 M, 0.12 M, and 26.4 M, 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. | |
| www.biorxiv.org | |
| 2020 | |
| Artículo | |
| https://www.biorxiv.org/content/10.1101/2020.04.14.041459v1.full.pdf | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
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