Biocomputational Analysis of Selected Compounds against Spike Protein: A Bioinformatics Approach

Bindu Madhava S; Sameer Sharma

Research Article

Austin Med Sci. 2021; 6(4): 1059.

Biocomputational Analysis of Selected Compounds against Spike Protein: A Bioinformatics Approach

Bindu Madhava S1 and Sameer Sharma2*

¹Department of Biochemistry, Kuvempu University, Karnataka, India

²Department of Bioinformatics, BioNome Private Limited, Bangalore, India

*Corresponding author: Sameer Sharma, Department of Bioinformatics, BioNome Private Limited, Bangalore, 560043, India

Received: October 27, 2021; Accepted: November 18, 2021 Published: November 25, 2021

Abstract

The main objective of the current study is to check the effectiveness of selected phytocompounds from the Chinese origin plant Cotinus coggygria in inhibiting the spike protein of Corona virus by assaying in the pharmacological tools and molecular docking analysis. Cotinus coggygria is a shrub which belongs to the family Anacardiaceae. The various phytochemicals of this compound shows the antiviral properties and some of the effective ones 3D structure was retrieved from PubChem and chemspider databases. The retrieved sequence was subjected to various bioinformatics tools such as SwissADME, PyRx, and Autodock for the molecular docking to check the effectiveness of selected phytocompounds in degrading the Spike protein of Corona virus. The results from the ADME and Autodock has proved the selected phytochemicals to have an antiviral property which is beneficial and effective against the Spike protein of Corona virus. Although Cotinus coggygria is known to show a medicinal property and is also being used as traditional medicine in various country, it has now been the spotlight for many researchers. The phytocompounds considered for this study has shown a better results in degrading the spike protein.

Keywords: Cotinus coggygria; Flavonoids; Spike protein; Molecular docking

Introduction

Cotinus coggygria, commonly known as European smoke tree is abundantly found in Southern Europe, Central Asia and Himalayas to northern China which belongs to the family Anacardiaceae.

It is a shrub which grows 5-7 m tall and has a multiple branches, Leaves are oval and green with a waxy glaucous sheen. This shrub produces numerous flower, with each flower having five pale yellow petals.

Scientific classification:

Higher classification: Smoketree

Kingdom: Plantae

Divison: Tracheophytes

Order: Sapindales

Family: Anacardiaceae

Genus: Cotinus

Species: coggygria

India is known to use traditional medicines from ancient times to treat many human diseases. Traditional medicines are generally extracted from various parts of the plants such as root, stem, flowers, leaves etc. Cotinus coggygria is one such plant which is known to have a potential phytochemicals which can be used to treat many group of diseases. This plant shows a bioactive properties for the diverse group of disorders. The phytochemicals present in this plant are generally treated as anti-inflammatory, anti-microbial, hepatoprotective, anti-hemorraghic agent in wound healing across the world and has shown a positive results in many cases. The dried leaf and twig of this plant is used in Chinese traditional medicine to eliminate dampness and heat and also as an antipyretic.

The various bioactive compounds are extracted from C. coggygria among which Myricetin, Fisetin, Rutin and Quercetin are known to have an antiviral property. The present studies shows the inhibiting activity of these phytochemicals against Novel Corona Virus [1].

Corona virus is a single stranded RNA virus which has a spherical lipid bilayer envelope [2]. Viral envelope has a Membrane (M), Envelope (E) and Spike (S) structural proteins embedded in it [3]. Membrane and Envelope protein accounts for the morphological aspects of the virus whereas Spike protein helps in the interaction with the other host cells [4]. And inside the envelope Nucleocapsid protein, a phosphoprotein rich in Arginine and Lysine is present attached to the single stranded RNA [5].

In the present study, the main focus is on Spike protein. Spike protein is the most distinguishable character of the corona virus in which on an average, there are about 74 surface spikes [6]. Each S protein is a trimer and has 2 subunits called S1 and S2 which are noncovalently linked to each other. S1 is the variable and critical part which forms the head of Spike protein and has the Receptor-Binding- Domain (RBD) [7].

Covid-19 has become a most dreadful infection which is seriously affecting human health. Till date there is no permanent drug available to treat this infection. The best possible way to prevent the infection is by using mask, washing hands, using sanitizer, sanitizing the infected places and maintaining social distance.

The current studies shows the degrading interaction of the bioactive molecules extracted from Cotinus coggygria with a spike protein of Covid-19.

Materials and Methods

Ligand preparation

All the selected phytochemicals of Cotinus coggygria were retrieved from PubChem databases [8] and Chemspider. And these structures were used for the molecular docking simulation against the Spike protein of novel corona virus. All the structures were fetched in the form of Standard Data Format and then converted into Protein Data Bank using PyMol.

Retrieval of receptors

7BNM a spike protein was used as a receptor against selected phytoligands to inhibit the activity of Corona virus. All the criteria for the receptors were analyzed by BLAST and PDB analysis.

Homology modelling for spike protein

The homology modelling for the Spike and Nucleocapsid protein was done by using SwissModel and Modeller. For SwissModel, the FASTA Sequence were retrieved from NCBI database and subjected into the modelling process. The homology of the selected template for the Spike and Nucleocapsid protein was above 90% with respect to percent identity.

ADMET and drug-likeness analysis

The admet and drug likeness analysis was analyzed through SwissADME and pre admet analysis with respect to five rule of Lipinski filter analysis [9]. To analyze the orally active drug, there are some standard criteria such as cLogP, molecular mass, hydrogen bond donor and acceptor [10]. All the physiochemical properties of phytocompounds were investigated or filtered by SwissADME, which is known for drug discovery tool.

Boiled-egg

BOILED-EGG is used to predict depend on gastrointestinal absorption and blood brain barrier for the development of drugs [11]. According to BOILED-Egg plot, if any compounds are rightfully placed in white region of eggs, the probability of GI absorption is higher and blood brain barrier is higher in case of compound correctly placed in yellow region. In this study, the analysis of the selected compounds for BOILED-Egg was done using Swiss-ADME server.

Molecular docking analysis

The objective of the molecular docking analysis is to assume or predict the interaction or inhibitory activity of selected phytocompounds in contrast to targeted Spike protein receptors. For Molecular docking, the binding affinity or docking score will give you to the all binding pores of molecules insides the catalytic sites of a protein which leads to the proper interaction between the molecules [12].

For the molecular docking, Autodock Vina, Patchdock, and PyRx (Virtual Docking Tool) were used to check the inhibitory activity of Phytocompounds with leads to the binding affinity and docking score [13]. Once the docking performed, all the hydrophobic interaction was investigated using PyMOl version 1.3 [14].

Results and Discussion

Ligands

All the three-dimensional structures of the selected phytocompounds were retrieved from the PubChem and chemspider databases and leads to the screening through FT Site Server.

Analysis of drug likeness

After completion of Lipinski filter analysis which exposed the rigidity and stability of all the selected phytocompounds and also listed out the compound’s property using ADME analysis.

Physiochemical properties of ligands:

Table 1.

Table 1: Physiochemical properties of ligands.




  
    Ligands
    Molecular    formula
    Molecular    weight
    Monoisotropic    mass
    Heavy    atom count
    Topological    polar surface area
  
  
    Fisetin
    C15H10O6
    286.24g/mol
    286.047738g/mol
    21
    107 Å2 
  
  
    Rutin
    C27H30O16
    610.5g/mol
    610.153385g/mol
    43
    266 Å2 
  
  
    Quercetin
    C15H10O7
    302.23g/mol
    302.042653g/mol
    22
    127 Å2



Table 1: Physiochemical properties of ligands.

Lipinski filter analysis:

Table 2.

Table 2: Lipinski filter analysis.




  
    Ligands
    Molecular    formula
    Hydrogen    bond Donor
    Hydrogen    bond Acceptor
    cLogP
    Molar    Refractivtiy
  
  
    Fisetin
    C15H10O6
    4
    6
    1.55
    76.01
  
  
    Rutin
    C27H30O16
    10
    16
    -1.12
    141.38
  
  
    Quercetin
    C15H10O7
    5
    7
    1.23
    78.03



Table 2: Lipinski filter analysis.

Admesar analysis:

Table 3.

Table 3: Admesar analysis.




  
    Ligands
    Blood    brain barrier
    GI    absorption
    Permeability    glycoprotein substrate
    Log S    (scale Insoluble < -10<Poorly<-6< Moderately <-    4<Soluble<-2 Very<0< Highly) [Water solubility]
  
  
    Fisetin
    No
    High
    No
    -3.35
  
  
    Rutin
    No
    Low
    Yes
    -3.3
  
  
    Quercetin
    No
    High
    No
    -3.16



Table 3: Admesar analysis.

Boiled egg

The prediction from Boiled Egg shows that Fisetin and Quercetin has high GI absorption while Rutin has low GI absorption (Figure 1).

Figure 1: Boiled Egg shows that Fisetin and Quercetin has high GI absorption while Rutin has low GI absorption. • Molecule 1 is Myricetin and has 1 Lipinski violation (H bond Donor is more than 5). • Molecule 2 is Fisetin and has no Lipinski violation. • Molecule 3 is Rutin and has 3 lipinski violation (Molecular mass is more than 500, H bond Donor is more than 5, H bond Acceptor is more than 10). • Molecule 4 is Quercetin and has no Lipinski violation.

    
    
    Figure 1: Boiled Egg shows that Fisetin and Quercetin has high GI absorption while Rutin has low GI absorption.
• Molecule 1 is Myricetin and has 1 Lipinski violation (H bond Donor is more than 5).
• Molecule 2 is Fisetin and has no Lipinski violation.
• Molecule 3 is Rutin and has 3 lipinski violation (Molecular mass is more than 500, H bond Donor is more than 5, H bond Acceptor is more than 10).
• Molecule 4 is Quercetin and has no Lipinski violation.

Molecular docking analysis

The results obtained from Molecular docking of the selected phytocompounds with Spike protein of corona virus shows that, most of the compounds are showing a better binding affinity which indicates a better drug quality to treat Corona virus. Quercetin shows the binding affinity of -7.5, Fisetin shows the binding affinity of -7.4 and Rutin shows the binding affinity of -7.5 (Table 4 and Figure 2).

Download PDF

Citation: Bindu Madhava S and Sharma S. Biocomputational Analysis of Selected Compounds against Spike Protein: A Bioinformatics Approach. Austin Med Sci. 2021; 6(4): 1059.

Home

Journal Scope

Editorial Board

Instruction for Authors

Submit Your Article