Chercheur invité
Projet de recherche
- Application des molécules naturelles à diverses maladies
Site internet personnel
- Page
- Adresse courriel : roger.gaudreault at umontreal.ca
Financement
- Divers
Articles en collaboration
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M. Haddad, R. Gaudreault, G. Sasseville, P. T. Nguyen, H. Wiebe, T. Van De Ven, et al., Molecular Interactions of Tannic Acid with Proteins Associated with SARS-CoV-2 Infectivity, International Journal of Molecular Sciences 23 (2022), doi:10.3390/ijms23052643.Résumé : The overall impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on our society is unprecedented. The identification of small natural ligands that could prevent the entry and/or replication of the coronavirus remains a pertinent approach to fight the coronavirus disease (COVID-19) pandemic. Previously, we showed that the phenolic compounds corilagin and 1,3,6-tri-O-galloyl-β-D-glucose (TGG) inhibit the interaction between the SARS-CoV-2 spike protein receptor binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 target receptor on the cell membrane of the host organism. Building on these promising results, we now assess the effects of these phenolic ligands on two other crucial targets involved in SARS-CoV-2 cell entry and replication, respectively: transmembrane protease serine 2 (TMPRSS2) and 3-chymotrypsin like protease (3CLpro) inhibitors. Since corilagin, TGG, and tannic acid (TA) share many physicochemical and structural properties, we investigate the binding of TA to these targets. In this work, a combination of experimental methods (biochemical inhibition assays, surface plasmon resonance, and quartz crystal microbalance with dissipation monitoring) confirms the potential role of TA in the prevention of SARS-CoV-2 infectivity through the inhibition of extracellular RBD/ACE2 interactions and TMPRSS2 and 3CLpro activity. Moreover, molecular docking prediction followed by dynamic simulation and molecular mechanics Poisson–Boltzmann surface area (MMPBSA) free energy calculation also shows that TA binds to RBD, TMPRSS2, and 3CLpro with higher affinities than TGG and corilagin. Overall, these results suggest that naturally occurring TA is a promising candidate to prevent and inhibit the infectivity of SARS-CoV-2. -
V. Binette, S. Côté, M. Haddad, P. T. Nguyen, S. Bélanger, S. Bourgault, et al., Corilagin and 1,3,6-Tri- -galloy-β-d-glucose: potential inhibitors of SARS-CoV-2 variants, Physical Chemistry Chemical Physics 23, 14873-14888 (2021). -
R. Gaudreault, V. Hervé, T. G. M. van de Ven, N. Mousseau, C. Ramassamy, Polyphenol-Peptide Interactions in Mitigation of Alzheimer’s Disease: Role of Biosurface-Induced Aggregation, Journal of Alzheimer's Disease 81, 33-55 (2021).Résumé : Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder, responsible for nearly two-thirds of all dementia cases. In this review, we report the potential AD treatment strategies focusing on natural polyphenol molecules (green chemistry) and more specifically on the inhibition of polyphenol-induced amyloid aggregation/disaggregation pathways: in bulk and on biosurfaces. We discuss how these pathways can potentially alter the structure at the early stages of AD, hence delaying the aggregation of amyloid-β (Aβ) and tau. We also discuss multidisciplinary approaches, combining experimental and modelling methods, that can better characterize the biochemical and biophysical interactions between proteins and phenolic ligands. In addition to the surface-induced aggregation, which can occur on surfaces where protein can interact with other proteins and polyphenols, we suggest a new concept referred as “confinement stability”. Here, on the contrary, the adsorption of Aβ and tau on biosurfaces other than Aβ- and tau-fibrils, e.g., red blood cells, can lead to confinement stability that minimizes the aggregation of Aβ and tau. Overall, these mechanisms may participate directly or indirectly in mitigating neurodegenerative diseases, by preventing protein self-association, slowing down the aggregation processes, and delaying the progression of AD. -
R. Gaudreault, N. Mousseau, Mitigating Alzheimer's Disease with Natural Polypenols: A Review, Current Alzheimer Research 16, 529-543 (2019).
