Microfluidic Diffusion Sizing Applied to the Study of Natural Products and Extracts That Modulate the SARS-CoV-2 Spike RBD/ACE2 Interaction
Jason Fauquet, Julie Carette, Pierre Duez, Jiuliang Zhang, Amandine Nachtergael
Molecules, doi:10.3390/molecules28248072
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 (R h ) and dissociation constant (K D ); the evolution of R h is monitored in the presence of increasing concentrations of the partner protein (ACE2); and the K D is determined through a binding curve experimental design. In a second time, with the protein partners present in equimolar amounts, the R h 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.
Author Contributions: Conceptualization, P.D. and A.N.; methodology, J.F.; investigation, J.F. and J.C.; resources, Laboratory of Pharmacognosy and Therapeutic chemistry form UMONS; data curation, J.F.; Visualization, J.Z., writing-original draft preparation, J.C.; writing-review and editing, J.C., A.N., J.F. and P.D. All authors have read and agreed to the published version of the manuscript. Funding: 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. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the..
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'abstract': '<jats:p>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.</jats:p>',
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