In silico exploration of phytocompounds from AYUSH-64 medicinal plants against SARS CoV-2 RNA-dependent RNA polymerase

Background: The AYUSH 64 formulation helps to treat mild to moderate cases of COVID-19. Although several drugs have been proposed to combat COVID-19, no medication is available for SARS-CoV-2 infection. The RNA-dependent RNA polymerase (RdRp) is the pivotal enzyme of SARS-CoV-2 replication, so it co...

Full description

Saved in:
Bibliographic Details
Main Authors: Srinivasulu Cheemanapalli, Ramanjaneyulu Golla, Sudhakar Pagidi, Seshapani Pantangi
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Journal of Ayurveda and Integrative Medicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0975947624001414
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846111791438888960
author Srinivasulu Cheemanapalli
Ramanjaneyulu Golla
Sudhakar Pagidi
Seshapani Pantangi
author_facet Srinivasulu Cheemanapalli
Ramanjaneyulu Golla
Sudhakar Pagidi
Seshapani Pantangi
author_sort Srinivasulu Cheemanapalli
collection DOAJ
description Background: The AYUSH 64 formulation helps to treat mild to moderate cases of COVID-19. Although several drugs have been proposed to combat COVID-19, no medication is available for SARS-CoV-2 infection. The RNA-dependent RNA polymerase (RdRp) is the pivotal enzyme of SARS-CoV-2 replication, so it could be considered a better drug target for experimental studies. Objective: The AYUSH-64 formulation plants exhibited multiple therapeutic properties; thus, the present study aims to screen the phytocompounds of these plants against SARS CoV2 RdRp to identify specific compounds that could potentially affect COVID-19 infection. Materials and methods: PatchDock and AutoDock tools were used for docking experiments. MD simulations and Density Functional Theory (DFT) calculations of protein-ligand Picroside-I and Remdesivir complexes were carried out in GROMACS v2019.4 and Gaussian 09 software, respectively. Results: Among the tested, five phytocompounds (Picroside I, Oleanolic acid, Arvenin I, II, and III) from AYUSH-64 medicinal plants showed possible binding with RdRp catalytic residues (Ser759, Asp760, and Asp761). Of these, Picroside I exhibited hydrogen bond interactions with NTP entry channel residues (Arg553 and Arg555). The MM-PBSA free energy, RMSD, Rg, PCA, and RMSF analysis suggested that the Picroside I complex showed stable binding interactions with RdRp in the 50 ns simulation. In addition to this, Picroside I revealed its robust and attractive nature toward the target protein, as confirmed by DFT. Conclusion: The results of this study have proposed that Picroside I from AYUSH 64 medicinal plant compounds was the selective binder of catalytic and NTP entry channel residues of SARS-CoV2 RdRp thereby; it may considered as a potential inhibitor of SARS-CoV2 RdRp.
format Article
id doaj-art-cabfcbd55f6f44b09e17eb83f71c99a7
institution Kabale University
issn 0975-9476
language English
publishDate 2024-11-01
publisher Elsevier
record_format Article
series Journal of Ayurveda and Integrative Medicine
spelling doaj-art-cabfcbd55f6f44b09e17eb83f71c99a72024-12-23T04:19:05ZengElsevierJournal of Ayurveda and Integrative Medicine0975-94762024-11-01156101026In silico exploration of phytocompounds from AYUSH-64 medicinal plants against SARS CoV-2 RNA-dependent RNA polymeraseSrinivasulu Cheemanapalli0Ramanjaneyulu Golla1Sudhakar Pagidi2Seshapani Pantangi3Survey of Medicinal Plants Unit, CCRAS - Regional Ayurveda Research Institute, Itanagar, Arunachal Pradesh, IndiaDepartment of Biochemistry, School of Allied Health Science, REVA University, Bangalore, India; Corresponding author. Department of Biochemistry, School of Allied Health Science, REVA University, Bangalore, India.Department of Chemical Sciences, Indian Institute of Science, Bangalore, IndiaDepartment of Microbiology, Sri Venkateswara University, Tirupati, IndiaBackground: The AYUSH 64 formulation helps to treat mild to moderate cases of COVID-19. Although several drugs have been proposed to combat COVID-19, no medication is available for SARS-CoV-2 infection. The RNA-dependent RNA polymerase (RdRp) is the pivotal enzyme of SARS-CoV-2 replication, so it could be considered a better drug target for experimental studies. Objective: The AYUSH-64 formulation plants exhibited multiple therapeutic properties; thus, the present study aims to screen the phytocompounds of these plants against SARS CoV2 RdRp to identify specific compounds that could potentially affect COVID-19 infection. Materials and methods: PatchDock and AutoDock tools were used for docking experiments. MD simulations and Density Functional Theory (DFT) calculations of protein-ligand Picroside-I and Remdesivir complexes were carried out in GROMACS v2019.4 and Gaussian 09 software, respectively. Results: Among the tested, five phytocompounds (Picroside I, Oleanolic acid, Arvenin I, II, and III) from AYUSH-64 medicinal plants showed possible binding with RdRp catalytic residues (Ser759, Asp760, and Asp761). Of these, Picroside I exhibited hydrogen bond interactions with NTP entry channel residues (Arg553 and Arg555). The MM-PBSA free energy, RMSD, Rg, PCA, and RMSF analysis suggested that the Picroside I complex showed stable binding interactions with RdRp in the 50 ns simulation. In addition to this, Picroside I revealed its robust and attractive nature toward the target protein, as confirmed by DFT. Conclusion: The results of this study have proposed that Picroside I from AYUSH 64 medicinal plant compounds was the selective binder of catalytic and NTP entry channel residues of SARS-CoV2 RdRp thereby; it may considered as a potential inhibitor of SARS-CoV2 RdRp.http://www.sciencedirect.com/science/article/pii/S0975947624001414SARS-CoV2RNA-Dependent RNA polymeraseAYUSH-64DockingMD simulationsPicroside I
spellingShingle Srinivasulu Cheemanapalli
Ramanjaneyulu Golla
Sudhakar Pagidi
Seshapani Pantangi
In silico exploration of phytocompounds from AYUSH-64 medicinal plants against SARS CoV-2 RNA-dependent RNA polymerase
Journal of Ayurveda and Integrative Medicine
SARS-CoV2
RNA-Dependent RNA polymerase
AYUSH-64
Docking
MD simulations
Picroside I
title In silico exploration of phytocompounds from AYUSH-64 medicinal plants against SARS CoV-2 RNA-dependent RNA polymerase
title_full In silico exploration of phytocompounds from AYUSH-64 medicinal plants against SARS CoV-2 RNA-dependent RNA polymerase
title_fullStr In silico exploration of phytocompounds from AYUSH-64 medicinal plants against SARS CoV-2 RNA-dependent RNA polymerase
title_full_unstemmed In silico exploration of phytocompounds from AYUSH-64 medicinal plants against SARS CoV-2 RNA-dependent RNA polymerase
title_short In silico exploration of phytocompounds from AYUSH-64 medicinal plants against SARS CoV-2 RNA-dependent RNA polymerase
title_sort in silico exploration of phytocompounds from ayush 64 medicinal plants against sars cov 2 rna dependent rna polymerase
topic SARS-CoV2
RNA-Dependent RNA polymerase
AYUSH-64
Docking
MD simulations
Picroside I
url http://www.sciencedirect.com/science/article/pii/S0975947624001414
work_keys_str_mv AT srinivasulucheemanapalli insilicoexplorationofphytocompoundsfromayush64medicinalplantsagainstsarscov2rnadependentrnapolymerase
AT ramanjaneyulugolla insilicoexplorationofphytocompoundsfromayush64medicinalplantsagainstsarscov2rnadependentrnapolymerase
AT sudhakarpagidi insilicoexplorationofphytocompoundsfromayush64medicinalplantsagainstsarscov2rnadependentrnapolymerase
AT seshapanipantangi insilicoexplorationofphytocompoundsfromayush64medicinalplantsagainstsarscov2rnadependentrnapolymerase