BREAKING! COVID-19 Research: Glycosaminoglycans Such As Heparin Could Emerge As New Antivirals For COVID-19 Disease
: Glycosaminoglycans are a class of polydisperse and heterogeneous natural occurring products currently used as pharmaceuticals and even in nutritional supplements.
Included among them are unfractionated heparin, low molecular weight heparins, and heparinoids, all of which are clinically approved as anticoagulants with excellent bioavailability, stability, and safety pharmacokinetic profiles.
Significantly, glycosaminoglycans and their derivatives (some may not possess any significant anticoagulant activity) represent an under-utilized antiviral drug category, despite showing broad-spectrum activity against a variety of different viruses.
Past research have demonstrated their antiviral properties against herpes viruses, flaviviruses, influenza virus, and human immunodeficiency virus (HIV).
Most importantly, they have demonstrated efficacy against the family of
viruses called Coronaviridae
, which includes SARS-associated coronaviruses
A new research study led by Dr Courtney Mycrof-West of Keele University and Dr Mark A. Skidmore of Keele University and the University of Liverpool show that Glycosaminoglycans such as Heparin could emerge as new antivirals for the COVID-19 disease. https://www.biorxiv.org/content/10.1101/2020.04.29.068767v1
The study indicated that Glycosaminoglycans can inhibit cell invasion by acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses, which supports the utilization of such therapeutics in the fight against coronavirus disease
Dr Skidmore said, "Glycosaminoglycans are generally well-tolerated and have been used successfully for many years with limited and manageable side effects.”
The medical researchers studied the ability of the SARS-CoV-2 Spike (S1) protein receptor-binding domain to interact with glycosaminoglycans, and how it influenced the central strategy of the virus to attach to host cells.
The researcher’s approach used circular dichroism spectroscopy, which detects changes in secondary protein structures that arise in a solution using ultraviolet radiation. Upon binding, any conformational changes are readily detected and quantified with the use of spectral deconvolution techniques.
The observed changes in the research demonstrated how glycosaminoglycans interacted with the SARS-CoV-2 S1 receptor binding domain and induced specific conformational changes within this region.
The study findings implied that SARS-CoV-2 S1 receptor binding domain interacts with not only unfractionated heparin and low molecular weight heparins, but also other members of the glycosaminoglycan family of carbohydrates.
Dr Skidmore added These research findings pave the way for future research into next-generation, tailor-made, glycosaminoglycan-based antiviral agents against SARS-CoV-2 and other members of the Coronaviridae
These new research findings prove to be critical, as conventional drug development processes are slow and not very efficient against emerging
threats such as the ongoing COVID-19 pandemic. This makes the repurposing of drugs already available a more viable alternative.
Dr Skidmore further added, “These glycosaminoglycans may prove to be an invaluable resource for next-generation, biologically active, antiviral agents that display negligible anticoagulant potential, whilst the former remains tractable to facile, chemical (and enzymatic) engineering strategies to ablate their anticoagulation activities. Such medical preparations will be pliant to routine administration parenterally, but also directly via the respiratory tract by using nebulized solutions that will not have a significant systemic absorption. This significantly implies that even some remnant anticoagulant activity of certain glycosaminoglycans would not pose a problem, and the preparations may be suitable for prophylaxis and for patients under mechanical ventilation.”
He concluded, “Such treatment approaches even if proved only moderately effective may substantially lessen the burden on health care settings globally, and aid in tackling this disease.”
The researchers are also collaborating with various regulatory agencies, institutions and hospitals to start clinical trials soon.
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