Molecular docking, molecular dynamic and drug-likeness studies of natural flavonoids as inhibitors for SARS-CoV-2 main protease (Mpro)

Listiana Oktavia; Praptiwi Praptiwi; Andria Agusta

Molecular docking, molecular dynamic and drug-likeness studies of natural flavonoids as inhibitors for SARS-CoV-2 main protease (Mpro)

Abstract

The emergence of the global pandemic COVID-19 lead to a huge demand for the therapeutic agent to combat the disease. Since the FDA approval of some of HIV-1 main protease inhibitors such as ritonavir lopinavir to treat COVID-19, the investigation of anti-HIV inhibitor to inhibit SARS-CoV-2 main protease (Mpro) is getting considerably much attention. This study evaluates the potency of sixteen selected natural flavonoids which were previously reported active to block HIV-1 protease as potential inhibitors of SARS-CoV-2 Mpro. The molecular docking and dynamic study were completed to know the binding affinity and stability of the protein-ligand complex via docking study along with molecular dynamic simulations. Moreover, drug-likeness was also evaluated through via ADMET evaluation. This study revealed robinin (6), a flavonol molecule with linked to galactose-rhamnose at C3 and rhamnose molecule at C7, exhibited the highest binding affinity (-9 kcal/mol) among others. The amino acids that interacted with robinin were Asn142; Gly143; Arg188; Thr190. The binding affinity of robinin surpassed the binding affinity of ritonavir (-7.7 kcal/mol) and lopinavir (-8.2 kcal/mol). The replacement of the hydroxyl group from the flavonoid skeleton at C- 7, C-4’ was proposed to affect the binding affinity. The free hydroxyl group particularly in A ring and the position of the hydroxyl group were important to improve the binding affinity. The molecular dynamic simulation showed the stability of Mpro-robinin during the simulation period. The ADME evaluation referring to Lipinski`s rule of 5 revealed that the flavonoids (2,5,6,9,10,13,14,15) show low oral bioavailability and absorption. Robinin exhibited a good drug- likeness score (value:1) with an unconcerned level of acute toxicity. From this study, it was concluded that robinin showed the most potent natural flavonoids studied to inhibit SASR-CoV-2 Mpro by both docking study and ADME/tox properties evaluation.

Keywords

References

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Details

Primary Language

English

Subjects

Pharmaceutical Chemistry

Journal Section

Research Article

Authors

Listiana Oktavia ^* This is me
Indonesia

Praptiwi Praptiwi This is me
Indonesia

Andria Agusta This is me
Indonesia

Publication Date

June 28, 2025

Submission Date

May 19, 2021

Acceptance Date

November 14, 2021

Published in Issue

Year 2021 Volume: 25 Number: 6

IZ

https://izlik.org/JA82DW24MZ

Cite

RIS / Bibtex

APA

Oktavia, L., Praptiwi, P., & Agusta, A. (2025). Molecular docking, molecular dynamic and drug-likeness studies of natural flavonoids as inhibitors for SARS-CoV-2 main protease (Mpro). Journal of Research in Pharmacy, 25(6), 998-1009. https://izlik.org/JA82DW24MZ

AMA

1.Oktavia L, Praptiwi P, Agusta A. Molecular docking, molecular dynamic and drug-likeness studies of natural flavonoids as inhibitors for SARS-CoV-2 main protease (Mpro). J. Res. Pharm. 2025;25(6):998-1009. https://izlik.org/JA82DW24MZ

Chicago

Oktavia, Listiana, Praptiwi Praptiwi, and Andria Agusta. 2025. “Molecular Docking, Molecular Dynamic and Drug-Likeness Studies of Natural Flavonoids As Inhibitors for SARS-CoV-2 Main Protease (Mpro)”. Journal of Research in Pharmacy 25 (6): 998-1009. https://izlik.org/JA82DW24MZ.

EndNote

Oktavia L, Praptiwi P, Agusta A (July 1, 2025) Molecular docking, molecular dynamic and drug-likeness studies of natural flavonoids as inhibitors for SARS-CoV-2 main protease (Mpro). Journal of Research in Pharmacy 25 6 998–1009.

IEEE

[1]L. Oktavia, P. Praptiwi, and A. Agusta, “Molecular docking, molecular dynamic and drug-likeness studies of natural flavonoids as inhibitors for SARS-CoV-2 main protease (Mpro)”, J. Res. Pharm., vol. 25, no. 6, pp. 998–1009, July 2025, [Online]. Available: https://izlik.org/JA82DW24MZ

ISNAD

Oktavia, Listiana - Praptiwi, Praptiwi - Agusta, Andria. “Molecular Docking, Molecular Dynamic and Drug-Likeness Studies of Natural Flavonoids As Inhibitors for SARS-CoV-2 Main Protease (Mpro)”. Journal of Research in Pharmacy 25/6 (July 1, 2025): 998-1009. https://izlik.org/JA82DW24MZ.

JAMA

1.Oktavia L, Praptiwi P, Agusta A. Molecular docking, molecular dynamic and drug-likeness studies of natural flavonoids as inhibitors for SARS-CoV-2 main protease (Mpro). J. Res. Pharm. 2025;25:998–1009.

MLA

Oktavia, Listiana, et al. “Molecular Docking, Molecular Dynamic and Drug-Likeness Studies of Natural Flavonoids As Inhibitors for SARS-CoV-2 Main Protease (Mpro)”. Journal of Research in Pharmacy, vol. 25, no. 6, July 2025, pp. 998-1009, https://izlik.org/JA82DW24MZ.

Vancouver

1.Listiana Oktavia, Praptiwi Praptiwi, Andria Agusta. Molecular docking, molecular dynamic and drug-likeness studies of natural flavonoids as inhibitors for SARS-CoV-2 main protease (Mpro). J. Res. Pharm. [Internet]. 2025 Jul. 1;25(6):998-1009. Available from: https://izlik.org/JA82DW24MZ