The Binding interaction analysis of phytoconstituents of Commiphora mukul with 3CLPro and PLPro enzymes of SARS-CoV-2 virus Compounds form C. mukul against 3CLPro and PLPro of SARS-CoV-2

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Published Sep 21, 2021
Rajasekhar Chinta Rajeswari Wai Jun Chen Aashika Amber Teoh Xian Ying Chung Choon Hoong Kuhashene

Abstract

 

Background

COVID-19 is a global health crisis that has a dramatic impact on not only people’s health and lives, but also their family, mental health, and the economy. The current treatment available for SARS-COV-2 infection include immunomodulators, convalescent plasma, glucocorticoids, antimalarial drugs, antiviral drugs [1]. Many vaccines have been marketed globally and the number of people getting vaccinated increasing day by day. However, the emerging multiple variants of the virus have become a formidable challenge for the research fraternity. Many existing drugs were tried against the viral infection but none of them gave promising outcomes. Despite the attempts and temporary usage of drugs for the treatment for Covid-19, the definite and promising treatment for Covid-19 is still under the process of discovery. The SARS-CoV-2 is a single-stranded and positive-sense virus with RNA inside that can produce two important enzymes namely, 3 chymotrypsin-like protease (3CLPro) [2] and papain-like protease (PLPro) [3]. 3CLPro is essential to cleave the polyproteins to make them functional. The active site of 3CLPro has a catalytic dyad of Cys-His homodimers. On the other hand, PLPro is a cysteine protease that recognizes the LXGG tetrapeptide motif found in between non-structural viral proteins (NSPs) [4,5] that are crucial for the life cycle of the virus. Considering their functional importance in the viral replication and lifecycle, both the enzymes are considered as targets for the structure-based design and discovery of drugs against SARS-CoV-2 infection.

Commiphora mukul is an ethnic and medicinal plant that secured a place in various therapies against diseases. It has many diverse chemical constituents such as sterols, volatile oils, mono, diterpenoids, and sesquiterpenoids in its oleoresin. The extract of C. mukul has been used to treat a variety of disorders such as dyslipidemia, obesity, inflammation, viral and bacterial infections [6].

However, the proposed In-silico study is an attempt to find new lead compounds from C. mukul and their possible role in inhibiting key enzymes of viral replication and the life cycle of the SARS-Cov-2 virus.

 

Methods: The 3D structures (3CLPro - PDB ID:4WY3; PLPro - PDB ID: 6WUU) of these proteins were retrieved from the RCSB database and the molecular structures of 34 phytoconstituents of C. mukul were drawn using ChemSketch tool and converted into a Protein Data Bank compatible format. Conformers were generated for molecular structures using the PatchDock server followed by molecular docking with the AutoDock Vina tool. Further, the ligands were subjected to ADME, drug-likeness, bioactivity predictions, and toxicity analysis using SwissADME, Molsoft, Molinspiration, and ProToxII online servers respectively. The visualization and analysis of the docked complexes were performed on Discovery Studio and all other prediction scores were tabulated.

Results: A total of 12 compounds were shortlisted out of 34 phytoconstituents based on their minimum binding energy with 3CLPro and PLPro enzymes. Their minimum binding energy ranged from -9.2 to -7.1 kcal/mol. Among these compounds, guggulsterol III showed the highest binding energy of -9.2 kcal/mol with PLPro (table 1), whereas the least binding energy is documented by 4, 17(20) -(Trans)-pregnadiene-3 with 3CLPro (-7.1 kcal/mol) (table 2). Quercetin galactoside made the maximum number of contacts (10) with PLPro enzyme (fig. 1) whereas, demethoxy-epiexcelsin and epiexcelsin formed the highest number of contacts with the 3CLPro enzyme (fig. 2). However, four ligands formed the lowest number of contacts with both 3CLPro and PLPro enzymes. All shortlisted ligands have fulfilled the criteria for the Lipinski rule of five except galactoside and guggulosterol V. Among the shortlisted ligands the LD50 values were ranged from 890 to 5000mg/kg body weight.

Conclusion: Current study has provided preliminary evidence for the binding abilities and possible bioactivities of shortlisted compounds present in oleoresin of the Commiphora mukul plant against the active sites of key enzymes (3CLPro and PLPro) of SARS-CoV-2 virus.

How to Cite

Chinta, R., Kalepu, R. ., Wai Jun Chen, Amber, A., Teoh Xian Ying, Chung Choon Hoong, & Kuhashene. (2021). The Binding interaction analysis of phytoconstituents of Commiphora mukul with 3CLPro and PLPro enzymes of SARS-CoV-2 virus: Compounds form C. mukul against 3CLPro and PLPro of SARS-CoV-2. SPAST Abstracts, 1(01). Retrieved from https://spast.org/techrep/article/view/1109
Abstract 60 |

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References
References
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Section
NB:Biology