Although most of us would like to forget about the pandemic as Canada eases its restrictions yet again, the threat of COVID-19 overwhelming the health-care system is still present as the country enters a sixth wave. A team of researchers from McGill, Institut national de la recherche scientifique (INRS), Université de Montréal, and Université du Québec à Montréal is still looking for suitable drug candidates to treat severe cases of COVID-19.
In a recent paper published in the International Journal of Molecular Sciences, the team shared their discovery that tannic acid (TA), a naturally occurring polyphenol compound, shows promising results in inhibiting the activity of the SARS-CoV2 virus. The researchers took a multidisciplinary approach to this collaborative project, with each contributor working on different experimental techniques, from molecular modelling simulations to enzyme assays in the lab.
Currently, the best weapon against the virus is the vaccine, which is a preventative measure. With mutative SARS-CoV2 variants like Omicron emerging with increased infectivity, there is a pressing need to find effective and accessible drug candidates.
Roger Gaudreault, one of the authors on this paper and a researcher at the Université de Montréal, explained why TA is an ideal drug candidate.
“As TA is a natural product obtained from plants, some of which are recognized for their use in food,” Gaudreault said in an interview with The McGill Tribune. “It appears that it will be a drug candidate of great relevance.”
According to Hannah Wiebe, a graduate student in McGill’s Department of Chemistry and one of the authors on the study, developing therapeutic drugs from natural products is actually not uncommon. Nearly 50 per cent of drugs developed in the last four decades are naturally derived.
The spike protein present on the outer membrane of the SARS-CoV2 virus facilitates its entry into human cells. It binds to the surface receptors, called ACE2, which are present on several tissue cells in humans. Both the spike protein and its ACE2 receptor serve as important targets for therapeutic drugs to prevent the entry of the virus into cells, stopping it from propagating throughout the body. Researchers found that, along with TA, two other natural polyphenol compounds called TGG and corilagin showed significant reduction in the binding between the spike protein and ACE2 receptors. Strikingly, TA reduced the binding by 95 per cent, the most effective of them all.
TA was also able to inhibit the enzymatic activity of other proteins involved in establishing an infection, which makes TA a very promising option as a multi-target drug.
Wiebe cautioned that their work is a very preliminary finding, limited to in vitro studies—meaning within an artificial environment—on isolated chemicals and proteins. It can often be hard to predict whether the same effects will be seen in real viruses and cells, or even COVID-19 patients, if the drug makes it to clinical trials.
The current antiviral drugs approved by the U.S. Food and Drug Administration include Remdesivir, Paxlovid and Molnupiravir, which have substantial side effects or very low rates of effectiveness. They are also extremely expensive and thus inaccessible to much of the world population.
Gaudreault emphasized that as with most polyphenols, TA’s efficacy is contingent on its bioavailability, which in turn depends on multiple factors such as the properties of the molecule itself, intestinal microbiota, pH values, and consumption alongside other compounds. He also said that while developing therapeutics, it is also important to consider the inter-variability between individual COVID-19 cases.
The discovery that TA might be able to inhibit the entry and multiplication of SARS-CoV2 in human cells paves the way for development of an efficient and accessible therapeutic drug. The main challenge now is to take this discovery from the lab to preclinical trials, and ultimately, to treat COVID-19 patients.