A potential anti-coagulant medication may prove effective for combating emerging variations of COVID-19.
In a groundbreaking multi-national study, researchers from the University of Queensland, Curtin University, Zucero Pharmaceuticals, QUT, the University of Liverpool, Keele University, the National Institute for Biological Standards and Control, and the Istituto di Ricerche Chimiche e Biochimiche 'G.Ronzoni' have identified a new binding site on the SARS-CoV-2 spike protein. This discovery could pave the way for potential broad-spectrum antiviral drugs for COVID-19 and other emerging viral threats.
The study, titled 'Evidence of a putative glycosaminoglycan binding site on the glycosylated SARS-CoV-2 spike protein N-terminal domain,' was published in the Computational and Structural Biotechnology Journal with the DOI 10.1016/j.csbj.2021.05.002.
QUT PhD researcher Zachariah Schuurs led the identification of this new binding site, which is located on the N-terminal domain (NTD) of the spike protein. The NTD facilitates the binding of heparan sulphate (HS) on cell surfaces, a crucial step in the virus's infection process.
The binding of HS to the SARS-CoV-2 spike protein is the first step in the virus's infection process. By targeting this new binding site with molecules like heparin (or heparin mimetics), researchers aim to stop the virus from binding to cells and infecting them. This could be a potential strategy to combat the virus and any emerging variants, especially those with positively charged mutations in the spike protein.
The study used both computational and experimental techniques to confirm the existence of this new binding site. Collaborators at the University of Liverpool and Keele University in the UK conducted laboratory experiments to support the hypothesis. The researchers used NCI Gadi and QUT Lyra supercomputers to model the interaction of HS and its inhibitor like heparin with the spike protein.
Most research on the SARS-CoV-2 spike protein has focused on the receptor-binding domain (RBD) and furin cleavage site. However, this new study expands our understanding of the virus by exploring other potential binding sites.
While COVID-19 vaccines are not widely accessible worldwide, this discovery offers a potential alternative strategy for treating the virus and its variants. Epidemiologists believe that persistent low-vaccine coverage in many countries will make it more likely for vaccine-resistant mutations to appear. In this context, broad-spectrum antiviral drugs like those derived from heparin could be crucial in combating the virus.
The study also suggests that molecules that mimic the 3D structure of heparin with different sulphur chemistry could be potential broad-spectrum antiviral drugs. These drugs could interact directly with the virus itself, providing a potential treatment option for a wide range of viruses, not just SARS-CoV-2.
In conclusion, this multi-national study has identified a new binding site on the SARS-CoV-2 spike protein that could be targeted with molecules like heparin for potential broad-spectrum antiviral drugs. This discovery could be a significant step forward in the fight against COVID-19 and other emerging viral threats.
