The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding

Many pathogens take advantage of the dependence of the host on the interaction of hundreds of extracellular proteins with the glycosaminoglycans heparan sulphate to regulate homeostasis and use heparan sulphate as a means to adhere and gain access to cells. Moreover, mucosal epithelia such as that o...

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Veröffentlicht in:bioRxiv
Hauptverfasser: Mycroft-West, Courtney J, Su, Dunhao, Elli, Stefano, Li, Yong, Guimond, Scott E, Miller, Gavin J, Turnbull, Jeremy E, Yates, Edwin A, Guerrini, Marco, Fernig, David G, Andrade De Lima, Marcelo, Skidmore, Mark A
Format: Paper
Sprache:Englisch
Japanisch
Veröffentlicht: Cold Spring Harbor Cold Spring Harbor Laboratory Press 29.04.2020
Cold Spring Harbor Laboratory
Ausgabe:1.2
Schlagworte:
Antiviral agents
Biochemistry
Circular dichroism
Coronaviruses
Gag protein
Glycosaminoglycans
Heparan sulfate
Heparin
Homeostasis
Mucin
Mucosa
Natural products
Polysaccharides
Respiratory tract
Serotonin S1 receptors
Surface plasmon resonance
heparin
COVID-19
Spike
SARS-CoV-2
surface plasmon resonance
molecular modelling
coronavirus
circular dichroism
S1, RBD
nCoV-19
ISSN:2692-8205, 2692-8205
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Zusammenfassung:Many pathogens take advantage of the dependence of the host on the interaction of hundreds of extracellular proteins with the glycosaminoglycans heparan sulphate to regulate homeostasis and use heparan sulphate as a means to adhere and gain access to cells. Moreover, mucosal epithelia such as that of the respiratory tract are protected by a layer of mucin polysaccharides, which are usually sulphated. Consequently, the polydisperse, natural products of heparan sulphate and the allied polysaccharide, heparin have been found to be involved and prevent infection by a range of viruses including S-associated coronavirus strain HSR1. Here we use surface plasmon resonance and circular dichroism to measure the interaction between the SARS-CoV- 2 Spike S1 protein receptor binding domain (SARS-CoV-2 S1 RBD) and heparin. The data demonstrate an interaction between the recombinant surface receptor binding domain and the polysaccharide. This has implications for the rapid development of a first-line therapeutic by repurposing heparin and for next-generation, tailor-made, GAG-based antivirals. Competing Interest Statement The authors have declared no competing interest.
Bibliographie:SourceType-Working Papers-1
ObjectType-Working Paper/Pre-Print-1
content type line 50
Competing Interest Statement: The authors have declared no competing interest.
ISSN:2692-8205
2692-8205
DOI:10.1101/2020.02.29.971093