Molecular docking studies of selected phytoconstituents from some indigenous medicinal plants against different targets of severe acute respiratory syndrome coronavirus 2

Vijaya Sachin Vichare; Snehal H Sutar; Manasi Pratap Rokade; Shashikant N Dhole; Vishnu P Choudhari

doi:10.4103/jpdtsm.jpdtsm_103_22

ORIGINAL ARTICLE

Year : 2023 | Volume : 2 | Issue : 1 | Page : 24-32

Molecular docking studies of selected phytoconstituents from some indigenous medicinal plants against different targets of severe acute respiratory syndrome coronavirus 2

Vijaya Sachin Vichare, Snehal H Sutar, Manasi Pratap Rokade, Shashikant N Dhole, Vishnu P Choudhari
Department of Quality Assurance, School of Pharmacy, MIT World Peace University, Pune, Maharashtra, India

Date of Submission	01-Dec-2022
Date of Decision	20-Jan-2023
Date of Acceptance	04-Feb-2023
Date of Web Publication	13-Mar-2023

Correspondence Address:
Vijaya Sachin Vichare
PES Modern College of Pharmacy (for Ladies), Pune, Maharashtra
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpdtsm.jpdtsm_103_22

Abstract

BACKGROUND: COVID-19 is a transmissible disease and propagated through a new strain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since December 2019 emerged from Wuhan, China, and this infection has widespread globally that causes to declare public health emergency in the whole world by the WHO. In this article, an attempt was made to recognize natural phytoconstituents from various indigenous medicinal plants, in order to utilize as a source against COVID-19 infections by virtue of molecular docking. The main focus of the study was molecular docking analysis of forty phytoconstituents from plants such as Tinospora cordifolia, Zingiber officinale, Azadirachta indica, Withania somnifera, Glycyrrhiza glabra, and Ocimum tenuiflorum with four different targets of SARS-CoV-2.
AIM AND OBJECTIVE: The aim of the study is to determine binding affinity of phytoconstitutents against different targets of SARS CoV2.
MATERIALS AND METHODS: Molecular docking was performed using VLifeMDS^® (version: 4.6. 08032021) and AutoDockTools.
RESULTS: Among forty phytoconstituents based on binding affinity, berberine and vicenin 2 showed the highest potential toward 3-chymotrypsin-like protease enzyme of SARS-CoV-2. Licorice and tinosporide had the potential to bind with the angiotensin-converting enzyme-2 of SARS-CoV-2. Rosmarinic acid also has a binding affinity toward papain-like protease (PLpro) enzyme of SARS-CoV-2. It has been also seen that isoorientin has ability to bind to RNA-dependent RNA polymerase of SARS-CoV-2.
CONCLUSION: Based on docking scores, the phytoconstituents from T. cordifolia, Z. officinale, A. Indica, W. somnifera, G. glabra, and O. tenuiflorum showed a good potential for binding to selected targets of SARS-CoV-2, and the antiviral activity of these plants can be scientifically supported by docking studies.

Keywords: COVID-19, molecular docking, phytoconstituents, severe acute respiratory syndrome coronavirus 2

How to cite this article:
Vichare VS, Sutar SH, Rokade MP, Dhole SN, Choudhari VP. Molecular docking studies of selected phytoconstituents from some indigenous medicinal plants against different targets of severe acute respiratory syndrome coronavirus 2. J Prev Diagn Treat Strategies Med 2023;2:24-32

How to cite this URL:
Vichare VS, Sutar SH, Rokade MP, Dhole SN, Choudhari VP. Molecular docking studies of selected phytoconstituents from some indigenous medicinal plants against different targets of severe acute respiratory syndrome coronavirus 2. J Prev Diagn Treat Strategies Med [serial online] 2023 [cited 2023 Mar 31];2:24-32. Available from: http://www.jpdtsm.com/text.asp?2023/2/1/24/371631

Introduction

The new public health pandemic COVID-19 is threatening to the world with the outbreak of novel coronavirus resulting in more than 4.5 million deaths worldwide.^[1] It has been declared as a public health emergency by the WHO.^[2] In December 2019, a new virus has been emerged in Wuhan, China, which spread across different countries that lead to public health emergency. It is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).^[3],[4] Coronaviruses have positive-sense single-stranded RNA viruses in their genome and have spike membrane of glycoprotein on their surfaces which resembles as a crown-like structure.^[5] The virus contains S-protein, papain-like protease (PL_pro), and RNA-dependent RNA polymerase (RdRp) which are involved in viral entry, replication, and immune response evasion. Drugs targeting these proteins have a great potential for inhibition.^[6] The spike protein directly interacts with peptidase domain of angiotensin-converting enzyme-2 (ACE-2) receptors which allows the entry of virus into the cell. This ACE-2 interaction with spike proteins could aid in producing vaccines or antivirals that can block the CoV infection by targeting ACE-2.^[7] The reported most common symptoms of SARS-CoV-2 infection are shortness of breath, fever, and cough since the epidemic, but now, new symptoms either as a result of squeal or viral infections are observed.^[8]

In the literatures, phytoconstituents from Tinospora cordifolia,^{[9],[10],[11],[12]} Ocimum tenuiflorum,^[13],[14] Withania somnifera,^[15],[16] G. glabra,^{[17],[18],[19]} Zingiber officinale,^[20],[21] and Azadirachta indica^[22],[23] have been reported for antiviral potential.

Molecular docking is a type of computational modeling that helps determine the optimal binding orientation of one molecule (for example, a ligand) to another (for example, a receptor) when they interact to form a stable complex.^[24] Because of its capacity to determine the conformation of small-molecule ligands within the appropriate target binding site with a high degree of accuracy, molecular docking is one of the most commonly utilized methods in structure-based drug design.^[25]

Targets 3-chymotrypsin-like protease (3CL_pro)_, RNA-dependent RNA polymerase (RdRp), human ACE-2, and PL_pro were selected based on previous studies.^{[26],[27],[28],[29],[30]}

In this study, to determine the binding affinity, we have tried to investigate the docking characteristics of forty selected phytoconstituents from traditional medicinal system against the four different targets of SARS-CoV-2.

Subjects and Methods

Computational tools for molecular docking from technology platform VLifeMDS^® (version: 4.6. 08032021) have been utilized for the current work. The steps involved in the current work are:

The details of work carried out in each step are as below:

Selection of target structures

The Protein Data Bank (PDB) structures for the selected targets were obtained from rcsb.org. These structures were further cleaned in the following steps:

Adding hydrogen
Completing incomplete residues
Adding missing residues
Removed unwanted chains and ligands.

Cleaning of the ligands

The chemical structures were drawn in a suitable 2D drawer and converted to 3D using VLifeMDS. The chemical structure was minimized using the MMFF force field and MMFF charges, with a GRMS criterion of 0.001. The conformers of the molecule were generated using a systematic method. More than 13000 conformers were generated and the top 500 conformers were selected for docking.

Identification of binding sites

The binding site for docking was selected using the analyze cavity option in VLifeMDS.

Docking study

The docking studies were performed using BIOPREDICTA module of VLifeMDS^® (version: 4.6. 08032021) A genetic algorithm docking was performed using the ligand flexible option and dock score as the fitness function.

The study consisted of four different targets whose PDB IDs are given in [Table 1] and structures of forty phytoconstituents along with source of plant are given in [Table 2].

Table 1: Targets and their Protein Data Bank IDs

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Table 2: Structures of ligand

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Results

The docking score of forty selected phytoconstituents from selected indigenous medicinal plants against four different targets of SARS-CoV-2 is given in [Table 3]. The docking result against 3CL_pro (PDB ID-1Z11) with phytoconstituents with the top five binding scores and interactions with ligand is given in [Table 4]. The docking result against RdRp (PDB ID-6M71) with the top five binding phytoconstituents is presented in [Table 5]. The docking result of human ACE-2 (PDB ID-1R42) with phytoconstituents having the top five binding scores and interactions with ligand is shown in [Table 6]. The docking results of PL_pro (PDB ID-4RNA) with phytoconstituents with the top five binding scores and interactions with ligand are expressed in [Table 7].

Table 3: Docking scores of forty selected phytoconstituents with targets

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Table 4: Docking result against 3-chymotrypsin-like protease (Protein Data Bank ID-1Z11)

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Table 5: Docking result against RNA-dependent RNA polymerase (Protein Data Bank ID-6M71)

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}

Table 6: Docking result against human angiotensin-converting enzyme 2 (Protein Data Bank ID-1R42)

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Table 7: Docking results of papain-like protease (Protein Data Bank ID-4RNA)

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Discussion

Docking result against (PDB ID-1Z11) with phytoconstituents demonstrated that out of the docked forty compounds, berberine showed the highest potential to bind to 3CL_pro enzyme. Berberine can potentially make an H-bonding interaction to bind GLN812: pi stacking (aromatic) interaction with PHE862A and hydrophobic interactions with ASN704A, LEU809A, GLN812A, ILE822A, ALA823A, and ILE826A. The binding scores of − 56.36 demonstrate strong bonding with the target. Vicenin 2 is one compound in the top five which showed an interaction with Asp808 which is one of the key substrate binding residues of 3CL_pro. Based on the docking scores and binding interactions, the top five compounds have a good potential to bind to 3CL_pro.

The docking results of RdRp (PDB ID-6M71) with the top five binding phytoconstituents demonstrated that out of the docked forty compounds, isoorientin showed maximum potential to bind to RdRp. Isoorientin can potentially make an H-bonding interaction with bind to LYS551A, ARG553A, ARG555A, and LYS621A, and hydrophobic interactions with LYS551A, ARG553A, and LYS621A. The binding scores of − 41.55 demonstrate strong bonding with the target. All the compounds show interactions with key binding site residues such as ARG555 or ARG553. Based on the docking scores and binding interactions, the top five compounds have a good potential to bind to RDRP receptor.

The docking results of human ACE-2 (PDB ID-1R42) demonstrated that out of the docked forty compounds, licorice showed potential to bind to ACE-2 enzyme. Licorice can potentially make an H-bonding interaction with bind to Gln442 and hydrophobic interactions with Thr445 and Ile446. The binding scores of −45.27 demonstrate strong bonding with the target. Tinosporaside is one compound in the top five which show an interaction with His345 which is one of the key binding residues between spike protein and ACE-2 receptor. Based on the docking scores and binding interactions, the top five compounds have a good potential to bind to ACE-2 receptor.

The docking results of PL_pro (PDB ID-4RNA) demonstrate that out of the docked forty compounds, rosmarinic acid shows the potential to bind to PL_pro from Middle East respiratory syndrome (MERS). Rosmarinic acid can potentially make a pi-stacking (aromatic) interaction with TRP190A and hydrophobic interactions with CYS321A. All the top five ligands show an interaction with residues close to the binding sites, thus suggesting the potential to inhibit the PL_pro enzyme.

Conclusion

COVID-19 is a life-threatening disease caused by SARS-CoV-2 and has turned into a gobal pandemic, which lockdown the whole world due to its widespread nature. The main focus of the study was molecular docking analysis of forty phytoconstituents from plants such as T. cordifolia, Z. officinale, A. Indica, W. somnifera, G. glabra, and O. tenuiflorum with four different targets of SARS-CoV-2. For that purpose, receptors 3CL_pro, RdRp, human ACE-2, and PL_pro were selected. Upon docking analysis of forty phytoconstituents, berberine has the highest potential to bind to the 3CL_pro enzyme along with vicenin and also has potential against the same enzyme. Liquorice and tinosporide have shown the highest binding affinity toward the ACE-2 receptors. Rosmarinic acid shows the highest binding affinity toward the enzyme involved in MERS, i.e., PL_pro. Along with that, isoorientin forms H bonding to the amino acid present on the receptors of RdRp with the highest potential. Based on docking scores, these phytoconstituents from T. cordifolia, O. tenuiflorum, and G. glabra showed a good potential for binding to selected targets of SARS-CoV-2 and antiviral activity of these plants can be supported by the above docking studies.

Limitations of the study

The study gives the primary information about binding affinity of the phytoconstituents with the targets based on the algorithm.

Acknowledgments

We thank Dr. Kundan B Ingle from VLife Sciences.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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