Chinese herbal compounds against SARS-CoV-2: Puerarin and quercetin impair the binding of viral S-protein to ACE2 receptor

Comput Struct Biotechnol J. 2020;18:3518-3527. doi: 10.1016/j.csbj.2020.11.010. Epub 2020 Nov 11.


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.

Keywords: ACE2; ACE2, Angiotensin-converting enzyme II; CHMs, Chinese herb medicines; COVID-19; Chinese herb medicine (CHM); KD, Equilibrium dissociation constants; Network pharmacology; PPI, Protein-protein interaction; RBD, Receptor-binding domain; SARS-CoV-2; SPR, Surface plasmon resonance; Surface plasmon resonance (SPR); TCM, Traditional Chinese medicine.