Unpublished conference/Abstract (Scientific congresses and symposiums)
Microfluidic Diffusional Sizing applied to the study of natural products and extracts that modulate the SARS-CoV-2 SpikeRBD/ACE2 interaction - Presentation
[en] The interaction between SARS-CoV-2 SpikeRBD and ACE2 proteins is a crucial step for host cell infection by the virus. Without it, the entire virion input mechanism is compromised. The aim of this study is to evaluate the capacity of various natural product classes to modulate this interaction. To do this, we applied a recently developed Microfluidic Diffusional Sizing (MDS) technique that allows to measure the interaction governing the protein-protein complexes via the measurement of the dissociation constant (Kd). In this method, a microfluidic chip chamber allows to monitor the diffusion of a fluorescently-labelled protein (SpikeRBD) between 2 laminar flows, giving a direct estimate of its hydrodynamic radius (Rh). 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 experiment design. In a second time, with the protein partners present in equimolar amounts, the Rh of the proteins complex was measured in the presence of different natural products. Five out of the nine natural products/extracts tested have shown modulatory activity: (i) the methanol extract of Chenopodium quinoa Willd seeds husk (50 µg/mL; saponins); (ii) ivermectin (1 nM), (iii) the flavonoids naringenin (1 µM) and quercetin (150 µM); and (iv) the ethanol extract of Rhei radix (Rheum palmatum L., Rheum officinale Baillon) (100 µg/mL; anthraquinones).
This rapid selection of effective modulators will be completed by Kd measurements, by a study of their effects on cells and by crystallographic studies that will elucidate their interactions with the complex SARS-CoV-2 SpikeRBD/ACE2. This will allow to better understand agents possibly preventive against 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
Language :
English
Title :
Microfluidic Diffusional Sizing applied to the study of natural products and extracts that modulate the SARS-CoV-2 SpikeRBD/ACE2 interaction - Presentation
Publication date :
03 December 2023
Event name :
Séminaire du projet WBI "TCM-Cyt"
Event organizer :
Dr. Xuebo Hu
Event place :
Wuhan, China
Event date :
3 décembre 2023
By request :
Yes
Audience :
International
Research unit :
M136 - Chimie thérapeutique et Pharmacognosie
Research institute :
R550 - Institut des Sciences et Technologies de la Santé
Funders :
project Wallonie-Bruxelles/China Fonds pour la Recherche Scientifique FNRS 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.