“People with AIDS need to follow drug tritherapy and they never treat themselves, they just prevent symptoms. And the treatment causes undesirable effects, mainly linked to inflammation and toxicity, “said the teacher-researcher at the INRS and co-director of the mixed inrs-UQAC research unit in sustainable health, Charles Gauthier.
With his team, he extracted a molecule present in large quantities in the birch bark, betulinic acid, which has long been known for its antiviral properties. The problem is that this molecule dissolves very badly in water, which made its use in medicine complicated, since the body has trouble absorbing it.
An innovative “chimerical” molecule
To overcome this drawback, the Charles Gauthier team has changed the betulinic acid molecule by adding a particular sugar, the Lewis X. This sugar is a type of carbohydrate close to those who define blood groups in humans.
This chemical modification made it possible to change the structure of the molecule extracted from the birch bark and to create a new chimerical compound (two heads): saponins.
This new molecule had never been described before in scientific literature. However, it represents an advantage that facilitates its use in antiviral treatments, first because it is more soluble in water and in biological environments than concrete acid, and especially because it is not toxic and therefore without danger for human cells.
“It will prevent the entry of viral particles within the immune system. It is not a treatment once you are infected, it is a potentially preventive treatment. Obviously, we are only at the beginning, in preclinical studies. ”
— Charles Gauhier, researcher at INRS
Lewis sugar will block one of the receptors on the cells of the immune system (called DC-Sign and L-SIG). These receptors are used by HIV to infect lymphocytes, and saponins will spread to CD4+cells, the main target of the virus.
“Our research shows that saponins are among the most effective ever discovered to block the HIV transfer mechanism to CD4+cells, even in very low doses,” continues Charles Gauthier, who is also an expert in carbohydrates and natural products.
“Although it is known that breast milk contains oligosaccharides capable of protecting newborns from HIV infection in the first months of breastfeeding, we are the first to demonstrate that saponins can inhibit the HIV entry route via the DC-Sign and L-Sign receptors,” adds the doctoral student in biology to INRS, Oscar Javier Gamboa Marin, first author of the study.
With a collaborator of Simon Fraser University, Ralph Pantophlet, Charles Gauthier’s team has tested these new molecules on five HIV strains for the moment.
Applicable to other viruses
“It is one of the main entrances of HIV that we block with these molecules. But this way can be used by other viruses too, such as the Ebola virus, the Sars-Cov-2 and the dengue virus, ”notes Charles Gauthier.
Thus, these saponins could then serve as a basis for the development of wide spectrum antiviral agents, since they are able to block the infection from the first contact with the virus, for example during sex in the case of HIV.
Saponins also have the distinction of muller, which could allow, in future work, to increase antiviral activity and improve their efficiency against HIV, in particular by facilitating their targeting towards cells affected by the virus.
It is still too early to create a drug product from these results, but in several years, this preventive treatment against HIV could take the form of a cream to apply locally on the genitals.
“There would be a way, in the future, to add something to this molecule to develop adjuvants of antiviral vaccines. This would boost the immune system while preventing viral infection, “said the researcher, indicating that it was the starting project at the base.
Simplify the steps
There are a dozen steps before achieving these saponine molecules, and Charles Gauthier would in particular like to simplify those surrounding the transformation of Lewis sugar, which includes three sugars (galactose, fucose and galactosamine).
It is fucose that has a main interaction with DC-Sign receptors, and researchers are therefore trying to create saponins, but only with fucose. The reduction of these steps would be an advantage for the industrial scaling of these molecules.
“We still have work. For example, simplifying these molecules, adding other groups, doing what is called relationships of antiviral activity structures to improve the efficiency of these components. But we still have a promising seeded compound for the rest of our work. ”
The other nerve of war is to find funding to carry out the research that remains to be done to finally hope to develop preventive treatment against HIV.
The conclusions of this work was published by the scientific journal Chemistry — A European Journal And will be presented next week to the scientific community as part of a congress in Poland.
