1. Chinese herbal compounds against SARS-CoV-2: Puerarin and quercetin impair the binding of viral S-protein to ACE2 receptor
- Author
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Min Li, Senbiao Fang, Liren Liu, Boyu Pan, Ya Pan, Yun Wang, Ju Zhang, and Han Liu
- Subjects
Drug ,PPI, Protein-protein interaction ,CHMs, Chinese herb medicines ,lcsh:Biotechnology ,media_common.quotation_subject ,Biophysics ,ACE2 ,Pharmacology ,Biochemistry ,Article ,Virus ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Structural Biology ,Puerarin ,lcsh:TP248.13-248.65 ,KD, Equilibrium dissociation constants ,Genetics ,heterocyclic compounds ,Receptor ,ComputingMethodologies_COMPUTERGRAPHICS ,030304 developmental biology ,media_common ,0303 health sciences ,SARS-CoV-2 ,Chemistry ,ACE2, Angiotensin-converting enzyme II ,COVID-19 ,Chinese herb medicine (CHM) ,Computer Science Applications ,Surface plasmon resonance (SPR) ,030220 oncology & carcinogenesis ,RBD, Receptor-binding domain ,TCM, Traditional Chinese medicine ,Kaempferol ,Quercetin ,PubChem ,SPR, Surface plasmon resonance ,Network pharmacology ,Biotechnology ,Systems pharmacology - Abstract
Graphical abstract, Highlights • Three CHM components with the potential against COVID-19 are identified using TCMSP. • SPR assay result shows good binding affinity of puerarin and quercetin to ACE2. • Puerarin and quercetin impairs the binding of viral S-protein to ACE2 receptor. • Quercetin can also directly bind to S-protein to exert an viral neutralizing effect. • Results from this study propose a prompt application of puerarin on COVID-19 patients., The outbreak of COVID-19 raises an urgent need for the therapeutics to contain the emerging pandemic. However, no effective treatment has been found for SARS-CoV-2 infection to date. Here, we identified puerarin (PubChem CID: 5281807), quercetin (PubChem CID: 5280343) and kaempferol (PubChem CID: 5280863) as potential compounds with binding activity to ACE2 by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Molecular docking analysis showed that puerarin and quercetin exhibit good binding affinity to ACE2, which was validated by surface plasmon resonance (SPR) assay. Furthermore, SPR-based competition assay revealed that puerarin and quercetin could significantly affect the binding of viral S-protein to ACE2 receptor. Notably, quercetin could also bind to the RBD domain of S-protein, suggesting not only a receptor blocking, but also a virus neutralizing effect of quercetin on SARS-CoV-2. The results from network pharmacology and bioinformatics analysis support a view that quercetin is involved in host immunomodulation, which further renders it a promising candidate against COVID-19. Moreover, given that puerarin is already an existing drug, results from this study not only provide insight into its action mechanism, but also propose a prompt application of it on COVID-19 patients for assessing its clinical feasibility.
- Published
- 2020