[en] The interaction between SARS-CoV-2 spike RBD and ACE2 proteins is a crucial step for host cell infection by the virus. Without it, the entire virion entrance mechanism is compromised. The aim of this study was to evaluate the capacity of various natural product classes, including flavonoids, anthraquinones, saponins, ivermectin, chloroquine, and erythromycin, to modulate this interaction. To accomplish this, we applied a recently developed a microfluidic diffusional sizing (MDS) technique that allows us to probe protein-protein interactions via measurements of the hydrodynamic radius (Rh) and dissociation constant (KD); the evolution of Rh is monitored in the presence of increasing concentrations of the partner protein (ACE2); and the KD is determined through a binding curve experimental design. In a second time, with the protein partners present in equimolar amounts, the Rh of the protein complex was measured in the presence of different natural products. Five of the nine natural products/extracts tested were found to modulate the formation of the protein complex. A methanol extract of Chenopodium quinoa Willd bitter seed husks (50 µg/mL; bisdesmoside saponins) and the flavonoid naringenin (1 µM) were particularly effective. This rapid selection of effective modulators will allow us to better understand agents that may prevent SARS-CoV-2 infection.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
FAUQUET, Jason ✱; Université de Mons - UMONS > Faculté de Médecine et de Pharmac > Service de Chimie thérapeutique et Pharmacognosie
Carette, Julie ✱; Université de Mons - UMONS > Faculté de Médecine et de Pharmac > Service de Chimie thérapeutique et Pharmacognosie
DUEZ, Pierre ; Université de Mons - UMONS > Faculté de Médecine et de Pharmac > Service de Chimie thérapeutique et Pharmacognosie
Zhang, Jiuliang ; College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
NACHTERGAEL, Amandine ; Université de Mons - UMONS > Faculté de Médecine et de Pharmac > Service de Chimie thérapeutique et Pharmacognosie
✱ These authors have contributed equally to this work.
Language :
English
Title :
Microfluidic Diffusion Sizing Applied to the Study of Natural Products and Extracts That Modulate the SARS-CoV-2 Spike RBD/ACE2 Interaction.
Publication date :
13 December 2023
Journal title :
Molecules
ISSN :
1420-3049
eISSN :
1420-3049
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
R550 - Institut des Sciences et Technologies de la Santé
Funders :
project Wallonie-Bruxelles/China F.R.S.-FNRS - Fonds de la Recherche Scientifique National Key R&D Program of China
Funding number :
CDR J.0058.21; 2021YFE0194000
Funding text :
This work was partly supported by Wallonie-Bruxelles International through the project Wallonie-Bruxelles/China (MOST) “Anti-inflammatory herbal medicines and their active components to fight the cytokine storm associated with COVID-19 diseases (TCM-Cyt) ”. This work was supported by the Fonds pour la Recherche Scientifique FNRS under grant N° CDR J.0058.21 “PlasmLip”, which contributed to the acquisition of the fluidity instrument. Veronica Taco is warmly thanked for her analysis of the Chenopodium quinoa husk extract and for giving us access to this sample; Veronica Taco is a scholarship holder from the Académie de Recherche et d’Enseignement Supérieur (ARES, Belgium). This work was also supported by the National Key R&D Program of China, 2021YFE0194000.
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