Supervisors info:
Alexios-Leandros Skaltsounis, Professor (Supervisor),National and Kapodistrian University of Athens
Faculty of Pharmacy, Department of Pharmacognosy and Natural Products Chemistry
Sofia Mitakou, Professor,National and Kapodistrian University of Athens, Faculty of Pharmacy ,Department of Pharmacognosy and Natural Products Chemistry
Maria Halabalaki, Assistant Professor, National and Kapodistrian University of Athens, Faculty of Pharmacy, Department of Pharmacognosy and Natural Products Chemistry
Summary:
The global epidemic caused by SARS-CoV-2, a novel coronavirus, has highlighted the critical need for improved antiviral methods. Natural products have received a lot of attention in the search for new treatment approaches because of their various bioactive components and possible antiviral capabilities. Natural products originating from Olea europaea have long been recognized for their health advantages.
Natural olive products, such as olive oil, olive leaf extract, and olive polyphenols, are high in bioactive compounds such oleuropein, hydroxytyrosol, and tyrosol. These chemicals have a variety of biological actions, such as antioxidant, anti-inflammatory, and antibacterial characteristics. Several components of olive natural products have been shown in recent research to have antiviral activity against a variety of viruses, including respiratory viruses like influenza and coronaviruses.
In the context of the COVID-19 pandemic, research has indicated that certain olive-derived compounds may interfere with crucial steps in the viral life cycle. These mechanisms include inhibition of viral entry by blocking spike protein interactions with host cell receptors, interference with viral replication, and modulation of the host immune response to reduce excessive inflammation and cytokine storms. Furthermore, olive polyphenols have demonstrated the ability to strengthen the body's defense mechanisms, potentially enhancing resistance to viral infections. With this conceptual framework in mind, the phytochemical segment of this thesis encompasses the design and implementation of five distinct isolation protocols aimed at extracting bioactive compounds from olive leaf extract and olive mill waste water. These compounds include oleuropein, oleoside, 11-methyl oleoside, secologanoside, and secoiridoid lactones. Furthermore, this research delves into elucidating the hydrolysis products derived from oleoside, employing both chemical and enzymatic methods. This exploration seeks to identify the most environmentally friendly and efficient approach for yielding secondary metabolites.
Combining synthetic molecules with natural products to enhance their antiviral properties is a promising approach in drug development. Molnupiravir, a synthetic nucleoside analog with antiviral properties, has gained attention as a potential treatment for COVID-19. In this thesis, a conjuction of natural olive oil products with molnupiravir is proposed to create a synergistic antiviral formulation. The primary mechanism of action of molnupiravir relies on its ability to mimic either a pseudo-cytidine or a pseudo-uridine, inducing mutagenesis in the viral RNA polymerase. Commencing with uridine, 5-methyluridine, and thymidine as foundational components, this thesis is dedicated to the development of three analogs that incorporate oleoside with their corresponding DNA bases via a one-pot three step synthetic route, while also investigating potential structure-activity relationships.
In conclusion, the synthetic-conjunction strategy presented herein offers a compelling hypothesis for the development of a novel antiviral therapy against COVID-19. By combining the synthetic precision of molnupiravir with the natural health-promoting properties of olive oil products, we anticipate the potential for a potent and well-tolerated treatment option for viral infections. Further research and validation with molecular docking studies and biological tests are essential to bring this synthetic approach to fruition.
Keywords:
natural products, pharmacognosy, semisynthesis,SARS-CoV-2
