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. 2020 Oct 15;15(10):e0240653.
doi: 10.1371/journal.pone.0240653. eCollection 2020.

Potential bioactive glycosylated flavonoids as SARS-CoV-2 main protease inhibitors: A molecular docking and simulation studies

Sabri Ahmed Cherrak  1 , Hafida Merzouk  1 , Nassima Mokhtari-Soulimane  1
Affiliations

Potential bioactive glycosylated flavonoids as SARS-CoV-2 main protease inhibitors: A molecular docking and simulation studies

Sabri Ahmed Cherrak et al. PLoS One. .

Abstract

A novel coronavirus responsible of acute respiratory infection closely related to SARS-CoV has recently emerged. So far there is no consensus for drug treatment to stop the spread of the virus. Discovery of a drug that would limit the virus expansion is one of the biggest challenges faced by the humanity in the last decades. In this perspective, to test existing drugs as inhibitors of SARS-CoV-2 main protease is a good approach. Among natural phenolic compounds found in plants, fruit, and vegetables; flavonoids are the most abundant. Flavonoids, especially in their glycosylated forms, display a number of physiological activities, which makes them interesting to investigate as antiviral molecules. The flavonoids chemical structures were downloaded from PubChem and protease structure 6LU7 was from the Protein Data Bank site. Molecular docking study was performed using AutoDock Vina. Among the tested molecules Quercetin-3-O-rhamnoside showed the highest binding affinity (-9,7 kcal/mol). Docking studies showed that glycosylated flavonoids are good inhibitors for the SARS-CoV-2 protease and could be further investigated by in vitro and in vivo experiments for further validation. MD simulations were further performed to evaluate the dynamic behavior and stability of the protein in complex with the three best hits of docking experiments. Our results indicate that the rutin is a potential drug to inhibit the function of Chymotrypsin-like protease (3CL pro) of Coronavirus.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. General flavonoid structure.
Fig 2
Fig 2
Structure of the compounds with highest score against Mpro active site a) Quercetin 3- Rhamnoside b) Myricetin 3-Rutinoside c) Rutin.
Fig 3
Fig 3. Binding pose of Quercetin -3 rhamnoside in the active site of SARS-CoV-2main protease.
Fig 4
Fig 4
Binding pose of N3 inhibitor: Docked (green) co-crystallized (cyan) at the active site of the SARS-CoV-2Mpro (superimposed structures).
Fig 5
Fig 5
Interaction of flavonoids at the active site of the SARS-CoV-2Mpro a) Quercetin -3 Rhamnose, b) Myricetin 3-rutinoside, c) Rutin.
Fig 6
Fig 6
RMSD and RMSF plots for Mpro complex with quercetin -3 rhamnoside (black), myricetin 3-rutinoside (red) and rutin (green) for 50 ns.
Fig 7
Fig 7
Rg and hydrogen bonds plots for Mpro complex with quercetin -3 rhamnose (black), myricetin 3-rutinoside (red) and rutine (green) for 50 ns.
See this image and copyright information in PMC

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