Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jan 15:891:173759.
doi: 10.1016/j.ejphar.2020.173759. Epub 2020 Nov 27.

Flavonols as potential antiviral drugs targeting SARS-CoV-2 proteases (3CLpro and PLpro), spike protein, RNA-dependent RNA polymerase (RdRp) and angiotensin-converting enzyme II receptor (ACE2)

Chaima Mouffouk  1 , Soumia Mouffouk  2 , Sara Mouffouk  3 , Leila Hambaba  3 , Hamada Haba  2
Affiliations
Review

Flavonols as potential antiviral drugs targeting SARS-CoV-2 proteases (3CLpro and PLpro), spike protein, RNA-dependent RNA polymerase (RdRp) and angiotensin-converting enzyme II receptor (ACE2)

Chaima Mouffouk et al. Eur J Pharmacol. .

Abstract

The novel coronavirus outbreak (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents the actual greatest global public health crisis. The lack of efficacious drugs and vaccines against this viral infection created a challenge for scientific researchers in order to find effective solutions. One of the promising therapeutic approaches is the search for bioactive molecules with few side effects that display antiviral properties in natural sources like medicinal plants and vegetables. Several computational and experimental studies indicated that flavonoids especially flavonols and their derivatives constitute effective viral enzyme inhibitors and possess interesting antiviral activities. In this context, the present study reviews the efficacy of many dietary flavonols as potential antiviral drugs targeting the SARS-CoV-2 enzymes and proteins including Chymotrypsin-Like Protease (3CLpro), Papain Like protease (PLpro), Spike protein (S protein) and RNA-dependent RNA polymerase (RdRp), and also their ability to interact with the angiotensin-converting enzyme II (ACE2) receptor. The relationship between flavonol structures and their SARS-CoV-2 antiviral effects were discussed. On the other hand, the immunomodulatory, the anti-inflammatory and the antiviral effects of secondary metabolites from this class of flavonoids were reported. Also, their bioavailability limitations and toxicity were predicted.

Keywords: 3CL(pro); ACE2; Flavonols; PL(pro); RdRp; SARS-CoV-2.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Structures of flavonols possessing COVID-19 antiviral effects.
Fig. 2
Fig. 2
Substitutions affecting the binding stability of flavonols to the 3CLpro.
Fig. 3
Fig. 3
Structures of narcissin and calendoflavoside.
Fig. 4
Fig. 4
Effects of the substitution of C-3' (B ring) on the binding stability of flavonols to the S protein.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Lagunas Rangel F.A. Neutrophil‐to‐lymphocyte ratio and lymphocyte‐to‐C‐reactive protein ratio in patients with severe coronavirus disease 2019 (COVID‐19): a meta‐analysis. J. Med. Virol. 2020 https://doi: 10.1002/jmv.25819 - PMC - PubMed
    1. Ai T., Yang Z., Hou H., Zhan C., Chen C., Lv W., Xia L. Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases. Radiology. 2020;296:E32–E40. https://doi:10.1148/radiol.2020200642 - DOI - PMC - PubMed
    1. Amaretti A., Raimondi S., Leonardi A., Quartieri A., Rossi M. Hydrolysis of the rutinose-conjugates flavonoids rutin and hesperidin by the gut microbiota and bifidobacteria. Nutrients. 2015;7:2788–2800. https://doi: 10.3390/nu7042788 - PMC - PubMed
    1. Annapurna A., Reddy C.S., Akondi R.B., Rao S.R. Cardioprotective actions of two bioflavonoids, quercetin and rutin, in experimental myocardial infarction in both normal and streptozotocin‐induced type I diabetic rats. J. Pharm. Pharmacol. 2009;61:1365–1374. https://doi: 10.1211/jpp/61.10.0014 - PubMed
    1. Antunes-Ricardo M., Gutiérrez-Uribe J.A., López-Pacheco F., Alvarez M.M., Serna-Saldívar S.O. In vivo anti-inflammatory effects of isorhamnetin glycosides isolated from Opuntia ficus-indica (L.) Mill cladodes. Ind. Crop. Prod. 2015;76:803–808. https://doi:10.1016/j.indcrop.2015.05.089 - DOI - PMC - PubMed

MeSH terms

Substances