Molecules from the same family as the anti-coagulant drug heparin may interfere with the ability of the COVID-19 virus’s spikes to bind to human cells. This could be used to treat people with severe effects of the virus and any emerging variants.
- New targetable site on the COVID-19 spike protein discovered
- Heparin-like molecules, a common anti-coagulant, could prevent the virus from infecting cells
- Low vaccine coverage in many countries means more vaccine-resistant mutations likely to appear.
QUT PhD researcher Zachariah Schuurs said the research team had identified a new binding site on the SARS-CoV-2 spike protein.
“Binding of the CoV-2 spike protein to heparan sulphate (HS) on cell surfaces is generally the first step in a cascade of interactions the virus needs to initiate an infection and enter the cell.
3D model showing heparan sulphate (green) binding to the N-terminal receptor binding domain of the SARS CoV-2 spike protein. Image created using 3D protein imager app The Protein Imager. Credit: Queensland University of Technology
“Most research has focused on understanding how HS interacts on the receptor-binding domain (RBD) and furin cleavage site of the SARS-CoV-2 virus’s spike protein, as these typically bind different types of drugs, vaccines and antibodies.
“We have identified a novel binding site on the N-terminal domain (NTD), a different area of the virus’s spike that facilitates the binding of HS. This helps to better understand how the virus infects cells. The NTD is also a part of the spike protein that frequently mutates.
“Some antibodies in the blood that neutralise the viruses bind to the same region of the NTD.
“Therefore, targeting the NTD site with molecules like heparin (or heparin mimetics), a known anti-coagulant drug similar to HS, is a possible strategy to stop the virus binding to cells and infecting them.”
Dr Neha Gandhi, from the QUT Centre for Genomics and Personalised Health, said COVID19 vaccines, although achieving success worldwide, were still far from being widely accessible.
“We need alternative antiviral strategies to prevent the spread of COVID-19 and treat infected people,” Dr Gandhi said.
“Epidemiologists believe that persistent low-vaccine coverage in many countries will make it more likely for vaccine-resistant mutations to appear.
Image credit: Tim Reckmann via Wikimedia (CC BY 2.0)
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“Variants of concern have already emerged in South Africa, the US, India and Brazil. In this regard, alternate antiviral strategies are strongly needed to prevent the spread of COVID-19 and to treat people with COVID-19.
“Most SARS-CoV-2 variants have acquired a positively charged mutation in the spike protein. Molecules like heparin and its mimetics are negatively charged and therefore, these molecules could be used to treat people with severe effects of the virus and any emerging variants.
“Our research indicates that molecules that mimic the 3D structure of heparin with different sulphur chemistry, might be potential broad-spectrum antiviral drugs for COVID-19 and other emerging viral threats via direct interaction with the virus itself.”
The multi-national study, “Evidence of a putative glycosaminoglycan binding site on the glycosylated SARS-CoV-2 spike protein N-terminal domain” published in the Computational and Structural Biotechnology Journal, used both computational and experimental techniques to confirm their finding.
The researchers used NCI Gadi and QUT Lyra supercomputers to model how HS and its inhibitors like heparin would interact with the spike protein.