Michel Chrétien, professor emeritus at the Faculty of Medicine, Université de Montréal.
Photo Credit: Amélie Philibert, Université de Montréal.
Scientific Frontline: Extended "At a Glance" Summary: Dicitriosides as Novel Antivirals
The Core Concept: Dicitriosides are newly identified triterpenoid compounds discovered in a plant extract that demonstrate potent, broad-spectrum antiviral activity against the Ebola virus and SARS-CoV-2. These rare natural molecules offer significant therapeutic potential at pharmacologically achievable concentrations.
Key Distinction/Mechanism: Previously, the antiviral effects of this plant extract were mistakenly attributed to isoquercitrin, a common flavonoid. Using advanced analytical methods, researchers pinpointed that these two obscure dicitriosides—comprising only 0.4% of the extract—were actually responsible for the activity and proved up to 25 times more effective than the original extract.
Major Frameworks/Components:
- Bioassay-Guided Isolation: A rigorous analytical approach used to trace and identify the microscopic amounts of active dicitriosides within a complex botanical mixture.
- Multilevel Residual Complexity Analysis: The methodological framework employed to reveal the origin of the nanomolar antiviral bioactives previously masked by 'isoquercitrin'.
- Triterpenoid Compounds: The specific chemical classification of the two newly discovered dicitriosides.
Branch of Science: Virology, Pharmacognosy (Natural Product Chemistry), Molecular Biology, and Pharmacology.
Future Application: These compounds open promising avenues for the development of new, broad-spectrum antiviral medications to treat current infectious diseases and better prepare for the rapid emergence of future pandemics.
Why It Matters: This discovery highlights that highly potent therapeutic agents can exist in nature in vanishingly small amounts. It emphasizes the critical need for long-term fundamental research, international scientific collaboration, and the precise chemical profiling of natural products in biomedical research.
Scientists at the Montreal Clinical Research Institute (IRCM), affiliated with the Université de Montréal, have identified a new family of natural molecules with strong antiviral activity, notably against the Ebola virus and SARS-CoV-2, the virus responsible for COVID-19.
The discovery comes at a time of renewed fears regarding the rapid emergence of new pandemics and highlights the ongoing search at the IRCM for novel antiviral agents derived from natural sources.
Led by Michel Chrétien, professor emeritus of medicine at the Université de Montréal, and Majambu Mbikay of the IRCM’s functional endoproteolysis laboratory, the research team detailed the development in a study published in the Journal of Natural Products, an American Chemical Society (ACS) publication.
As early as 2016 and again in 2020, IRCM researchers demonstrated that a plant extract rich in isoquercitrin—a flavonoid found in many plants—exhibited strong antiviral activity in the laboratory.
One critical question, however, remained: Was this effect truly due to isoquercitrin itself, or to compounds present in very small amounts within the extract?
To resolve this puzzle, Mbikay and his research assistant Annie Roy went looking for the proverbial “needle in the haystack,” an effort that required nearly thirty months of intensive research.
For help, they brought in Guido F. Pauli, a chemist and leading expert in natural products at the University of Illinois Chicago, and Logan Banadyga, director of the Department of Molecular Virology at Canada’s National Microbiology Laboratory in Winnipeg.
Two rare but highly potent molecules
Using advanced analytical methods and a rigorous, bioassay-guided approach, the research team demonstrated that the antiviral activity did not originate from isoquercitrin itself, but rather from two previously unknown triterpenoid compounds.
Though present at only 0.4 percent of the analyzed extract, these newly identified molecules, named dicitriosides, proved to be up to twenty-five times more active than the original extract against the Ebola virus and SARS-CoV-2 under experimental conditions.
Consequently, the molecules demonstrated efficacy at pharmacologically achievable concentrations.
“This discovery illustrates how compounds present in vanishingly small amounts in nature can have major therapeutic potential,” said Mbikay. “It also underscores the importance of carefully examining the true composition of natural products used in biomedical research.”
“Although this work is still at the preclinical stage, it opens promising avenues for the discovery of new broad-spectrum antivirals derived from natural products,” the scientists state in their study.
“No one knows when the next pandemic will occur, but one thing is certain: we must be prepared,” added Chrétien.
“These results demonstrate the importance of long-term fundamental research and international collaboration in anticipating the public health challenges of the future.”
Published in journal: Journal of Natural Products
Authors: Daniela Rebollar-Ramos, Annie V. Roy, J. Brent Friesen, Guy Harris, Shao-Nong Chen, Michael Chan, Shihua He, Guodong Liu, Wenjun Zhu, Logan Banadyga, James B. McAlpine, Michel Chrétien, Majambu Mbikay, and Guido F. Pauli
Source/Credit: Université de Montréal
Reference Number: vi043026_01