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. 2021 Jul;39(10):3449-3458.
doi: 10.1080/07391102.2020.1766572. Epub 2020 May 20.

Identification of bioactive molecules from tea plant as SARS-CoV-2 main protease inhibitors

Vijay Kumar Bhardwaj  1   2   3 , Rahul Singh  1   2 , Jatin Sharma  1   2 , Vidya Rajendran  2 , Rituraj Purohit  1   2   3 , Sanjay Kumar  2
Affiliations

Identification of bioactive molecules from tea plant as SARS-CoV-2 main protease inhibitors

Vijay Kumar Bhardwaj et al. J Biomol Struct Dyn. 2021 Jul.

Abstract

The SARS-CoV-2 is the causative agent of COVID-19 pandemic that is causing a global health emergency. The lack of targeted therapeutics and limited treatment options have triggered the scientific community to develop new vaccines or small molecule therapeutics against various targets of SARS-CoV-2. The main protease (Mpro) is a well characterized and attractive drug target because of its crucial role in processing of the polyproteins which are required for viral replication. In order to provide potential lead molecules against the Mpro for clinical use, we docked a set of 65 bioactive molecules of Tea plant followed by exploration of the vast conformational space of protein-ligand complexes by long term molecular dynamics (MD) simulations (1.50 µs). Top three bioactive molecules (Oolonghomobisflavan-A, Theasinensin-D, and Theaflavin-3-O-gallate) were selected by comparing their docking scores with repurposed drugs (Atazanavir, Darunavir, and Lopinavir) against SARS-CoV-2. Oolonghomobisflavan-A molecule showed a good number of hydrogen bonds with Mpro and higher MM-PBSA binding energy when compared to all three repurposed drug molecules. during the time of simulation. This study showed Oolonghomobisflavan-A as a potential bioactive molecule to act as an inhibitor for the Mpro of SARS-CoV-2.

Keywords: COVID-19; SARS-CoV-2; bioactive molecules; main protease.

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Figures

Figure 1.
Figure 1.
2-D interactions of SARS-CoV-2 Mpro protein with bio-actives (a) Oolonghomobisflavan-A (b) Theasinensin-D, and (c) Theaflavin-3-O-gallate.
Figure 2.
Figure 2.
2-D Interactions of SARS-CoV-2 Mpro protein with FDA approved drugs (a) Atazanavir (b) Darunavir, and (c) Lopinavir.
Figure 3.
Figure 3.
RMSD of backbone C-α atoms of complexes with (a) bioactives: Oolonghomobisflavan-A (black), Theasinensin-D (Red), and Theaflavin-3-O-gallate (green). (b) FDA approved drugs, Atazanavir (black), Darunavir (red), and Lopinavir (green).
Figure 4.
Figure 4.
Hydrogen bond profiles of the Mpro complexes having with (a) bioactives: Oolonghomobisflavan-A (black), Theasinensin-D (Red), and Theaflavin-3-O-gallate (green). (b) FDA approved drugs, Atazanavir (black), Darunavir (red), and Lopinavir (green).
Figure 5.
Figure 5.
Graphical representation of the Delta_E_Binding free energy kJ/mol showing (a) Bio-actives, Oolonghomobisflavan-A (black), Theasinensin-D (Red), and Theaflavin-3-O-gallate (green). (b) FDA approved drugs, Atazanavir (blue), Darunavir (pink), and Lopinavir (yellow).
Figure 6.
Figure 6.
Graphical representation of per residue contribution plot for (a) Bio-actives, Oolonghomobisflavan-A (black), Theasinensin-D (Red), and Theaflavin-3-O-gallate (green). (b) FDA approved drugs, Atazanavir (Cyan), Darunavir (yellow), and Lopinavir (pink).
See this image and copyright information in PMC

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