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Current Computer-Aided Drug Design

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ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

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Research Article

Revisiting the South Indian Traditional Plants against Several Targets of SARS-CoV-2 - An in silico Approach

Author(s): Srikanth Jupudi*, Srikala Rajala, Narasimha Rao Gaddam, Gomathi Swaminathan, Jaya Preethi Peesa, Kalirajan Rajagopal and Mohammed Afzal Azam

Volume 19, Issue 3, 2023

Published on: 19 January, 2023

Page: [202 - 233] Pages: 32

DOI: 10.2174/1573409919666221230105758

Price: $65

Abstract

Background: The south Indian Telugu states will celebrate a new year called ‘Ugadi’ which is a south Indian traditional festival. The ingredients used in ugadi pachadi have often also been used in food as well as traditional Ayurveda and Siddha medicinal preparations. Coronaviruses (CoVs) are a diverse family of enveloped positive-sense single-stranded RNA viruses which can infect humans and have the potential to cause large-scale outbreaks.

Objective: Considering the benefits of ugadi pachadi, we investigated the binding modes of various phytochemical constituents reported from its ingredients against five targets of SARS-CoV-2.

Methods: Flexible-ligand docking simulations were achieved through AutoDock version 1.5.6. Following 50ns of molecular dynamics simulation using GROMACS 2018.1 software and binding free energy (ΔGbind) of the protein-ligand complexes were calculated using the g_mmpbsa tool. ADME prediction was done using Qikprop of Schrodinger.

Results: From the molecular docking and MM/PBSA results compound Eriodictin exhibited the highest binding energy when complexed with nucleocapsid N protein (6M3M) (-6.8 kcal/mol, - 82.46 kJ/mol), bound SARS-CoV-2-hACE2 complex (6M0J) (-7.4 kcal/mol, -71.10 kJ/mol) and Mpro (6XR3) (-8.6 kcal/mol, -140.21 kJ/mol). Van der Waal and electrostatic energy terms highly favored total free energy binding.

Conclusion: The compounds Eriodictin, Vitexin, Cycloart-3, 24, 27-triol, Agigenin, Mangiferin, Mangiferolic acid, Schaftoside, 27-Hydroxymangiferonic acid, Quercetin, Azadirachtol, Cubebin, Isomangiferin, Isoquercitrin, Malicarpin, Orientin and procyanidin dimer exhibited satisfactory binding energy values when compared with standard molecules. The further iterative optimization of high-ranked compounds following validation by in vitro and in vivo techniques assists in discovering therapeutic anti-SARS-CoV-2 molecules.

Keywords: Ugadi pachadi, SARS-CoV-2, molecular docking, molecular dynamics, MM/PBSA, ADME.

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