Innovative, nontoxic molecules developed by a research team at the Institut national de la recherche scientifique (INRS) in Quebec, Canada, could pave the way for new safe and effective antiviral therapies for prevention and treatment purposes.
The researchers note there could be natural compounds with antiviral properties, particularly against the human immunodeficiency virus (HIV) that causes AIDS.
Betulinic acid has long been recognised in medical and scientific communities for its antiviral potential. This molecule, found in various plants, is especially abundant in the bark of white birch trees—a common byproduct of the forestry industry. However, the use of betulinic acid and some of its derivatives in medicine has been limited by a major drawback: the molecules are poorly soluble in water. This limits their absorption by the body and complicates their use in medicine.
A discovery by INRS Professor Charles Gauthier’s team, part of the INRS-UQAC Joint Research Unit in Sustainable Health, could significantly unlock the potential of this molecule. Their findings were recently published in Chemistry – A European Journal.
In their research, Gauthier’s team studied two natural molecules: betulinic acid and echinocystic acid. Both belong to a family of compounds known as triterpenes and share a similar chemical structure.
The researchers chemically modified these molecules using a novel, controlled method by attaching a specific sugar called Lewis X. This sugar is structurally similar to those that define human blood groups. The modification resulted in new chimeric compounds known as “saponins.”
These saponins had never been described in scientific literature before. They offer several advantages for potential antiviral use: they are significantly more water-soluble than triterpenes, they dissolve well in biological environments, and unlike similar substances that can be toxic, they are safe for human cells and mice.
Most importantly, they effectively block HIV activity. The team observed that saponins prevent the virus from using certain carbohydrate-specific proteins, known as Lewis-binding proteins, found on immune cells called DC-SIGN and L-SIGN, to spread to CD4+ cells, the main targets of HIV.
“Our results show that these are among the most potent monovalent inhibitors ever identified for blocking this HIV transfer mechanism, even when used at very low concentrations,” said Gauthier, who specializes in chemistry of carbohydrates and natural products. He is also a member of the Pasteur Network.
These chimeric molecules capable of blocking viral entry into immune cells—a critical step in infection—are a first of their kind. Saponins could serve as a foundation for developing broad-spectrum antiviral agents that block infection at the earliest stage, such as during sexual transmission of HIV.
“While it’s known that human breast milk contains oligosaccharides that protect infants from HIV infection during early breastfeeding, we are the first to demonstrate that saponins can inhibit HIV entry via DC-SIGN and L-SIGN receptors,” said doctoral student in biology at INRS and lead author Oscar Javier Gamboa Marin.
“Despite progress in this field, very few studies have focused on inhibiting DC-SIGN and L-SIGN using Lewis-type carbohydrates.”
Another promising feature of saponins is their ability to spontaneously form structures called micelles or to integrate into liposomes. This could further enhance their antiviral effectiveness, particularly through improved targeting of virus-infected cells, and holds out promising research potential.
Moreover, since DC-SIGN and L-SIGN proteins are also exploited by other dangerous viruses such as Ebola, dengue, and SARS-CoV-2, saponins open new avenues for developing broad-spectrum antiviral agents against these diseases.
Jim Cornall is editor of Deeptech Digest and publisher at Ayr Coastal Media. He is an award-winning writer, editor, photographer, broadcaster, designer and author. Contact Jim here.
