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

Abstract

Many pathogens take advantage of the dependence of the host on the interaction of hundreds of extracellular proteins with the glycosaminoglycans heparan sulfate to regulate homeostasis and use heparan sulfate 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 sulfated. Consequently, the polydisperse, natural products of heparan sulfate 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.

The role of growth factor receptors in viral infections: An opportunity for drug repurposing against emerging viral diseases such as COVID‐19?

“…37 Together, these data on coronaviruses suggest that SARS-Cov2 is also likely to bind to HSPG; preliminary data have recently been released that reinforce this hypothesis. 38 In this study, the authors used 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. 38 The data strongly suggested an interaction between the recombinant surface receptor binding domain of the virus and HS.…”

“…38 In this study, the authors used 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. 38 The data strongly suggested an interaction between the recombinant surface receptor binding domain of the virus and HS. The therapeutic targeting of HSPGs thus appears a relatively straightforward way to inhibit the infectivity of SARS-Cov2.…”

“…Because coronaviruses have been shown to bind to HS to enter target cells, 35,36 it can be hypothesized that heparin should act to prevent cell attachment of SARS-CoV-2. Preliminary data have indicated that indeed heparin does bind to the surface protein (spike) S1 of this virus 38 and may therefore be therapeutic for COVID-19.…”

Can Nebulised Heparin Reduce Time to Extubation in SARS-CoV-2 (CHARTER Study) – Protocol

“…A recent study demonstrated that the SARS-CoV-2 Spike S1 protein receptor binding domain attaches to unfractionated heparin and undergoes conformational change as a result. 64 Previous studies demonstrated that unfractionated heparin prevented SARSassociated coronavirus and other coronavirus strains from invading mammalian cells. [65][66][67][68][69][70] Safety and tolerability of nebulised heparin APTT.…”

Reply to Rheumatologists’ perspective on coronavirus disease 19: is heparin the dark horse for COVID-19?

“…One of the mechanisms of inhibition of cellular entry of SARS coronavirus is via lactoferrin binding [4]. It has shown that even the spike protein S1 of the SARS-CoV-2 undergoes a conformational change on exposure to heparin [5]. Thus, heparin might inhibit cellular entry of the virus.…”