Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 94 (6), 2023-2030

Characteristics of Flavonoids as Potent MERS-CoV 3C-like Protease Inhibitors

Affiliations

Characteristics of Flavonoids as Potent MERS-CoV 3C-like Protease Inhibitors

Seri Jo et al. Chem Biol Drug Des.

Abstract

Middle East respiratory syndrome-coronavirus (MERS-CoV) is a zoonotic virus transmitted between animals and human beings. It causes MERS with high mortality rate. However, no vaccine or specific treatment is currently available. Since antiviral activity of some flavonoids is known, we applied a flavonoid library to probe inhibitory compounds against MERS-CoV 3C-like protease (3CLpro). Herbacetin, isobavachalcone, quercetin 3-β-d-glucoside and helichrysetin were found to block the enzymatic activity of MERS-CoV 3CLpro. The binding of the four flavonoids was also confirmed independently using a tryptophan-based fluorescence method. The systematic comparison of the binding affinity of flavonoids made it possible to infer their scaffolds and functional groups required to bind with MERS-CoV 3CLpro. An induced-fit docking analysis revealed that S1 and S2 sites play a role in interaction with flavonoids. The experimental and computational study showed that flavonol and chalcone are favourite scaffolds to bind with the catalytic site of MERS-CoV 3CLpro. It was also deduced that some flavonoid derivatives with hydrophobic or carbohydrate attached to their core structures have a good inhibitory effect. Therefore, we suggest that flavonoids with these characteristics can be used as templates to develop potent MERS-CoV 3CLpro inhibitors.

Keywords: FRET; MERS-CoV; MERS-CoV 3CLpro; flavonoid; inhibitory compounds.

Similar articles

See all similar articles

Cited by 1 article

References

REFERENCES

    1. Chuck, C. P., Chow, H. F., Wan, D. C., & Wong, K. B. (2011). Profiling of substrate specificities of 3C-like proteases from group 1, 2a, 2b, and 3 coronaviruses. PLoS ONE, 6(11), e27228.
    1. de Wit, E., van Doremalen, N., Falzarano, D., & Munster, V. J. (2016). SARS and MERS: Recent insights into emerging coronaviruses. Nature Reviews Microbiology, 14, 523-534. https://doi.org/10.1038/nrmicro.2016.81
    1. Erbel, P., Schiering, N., D'Arcy, A., Renatus, M., Kroemer, M., Lim, S. P., … Hommel, U. (2006). Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus. Nature Structural & Molecular Biology, 13, 372-373.
    1. Fehr, A. R., & Perlman, S. (2015). Coronaviruses: An overview of their replication and pathogenesis. Methods in Molecular Biology, 1282, 1-23.
    1. Frabasile, S., Koishi, A. C., Kuczera, D., Silveira, G. F., Verri, W. A. Jr, Duarte Dos Santos, C. N., & Bordignon, J. (2017). The citrus flavanone naringenin impairs dengue virus replication in human cells. Scientific Reports, 7, 41864. https://doi.org/10.1038/srep41864

LinkOut - more resources

Feedback