Login Register Cart 0
Generic placeholder image

Current Pharmacogenomics and Personalized Medicine

Editor-in-Chief

ISSN (Print): 1875-6921
ISSN (Online): 1875-6913

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

The TP53 Gene and COVID-19 Virus: A Correlation Analysis

Author(s): C. Lakshmi Anand* and P.K. Krishnan Namboori

Volume 19, Issue 1, 2022

Published on: 02 August, 2022

Page: [53 - 63] Pages: 11

DOI: 10.2174/1875692119666220617160537

Price: $65

Abstract

Aim: This study aimed to discover the most effective anti-cancer medicine for cancer patients infected with SARS-CoV-2.

Background: The correlation between TP53 and SARS-CoV-2 was examined using biomolecular networking analysis.

Objective: Cancer patients with TP53 gene mutations are more likely to be infected with the SARS-CoV-2 virus since it is the most frequently mutated tumor suppressor gene in human cancer. The main goal of this study is to discover the most effective and efficient anti-cancer therapy for patients with SARS-CoV-2 infection.

Materials and Methods: Topp gene analysis was used to prioritize candidate genes based on molecular function, biological process, and pathway analysis. Biomolecular networking was carried out using Cytoscape 2.8.2. The protein-protein interaction network was used to identify the functionally associated proteins. The protein-drug interaction network was used to observe the molecular therapeutic efficiency of drugs. The network was further analyzed using CytoHubba to find the hub nodes. The molecular docking was used to study the proteinligand interaction, and the protein-ligand complex was further evaluated through molecular dynamic simulation to determine its stability.

Results: Functionally relevant genes were prioritized through Toppgene analysis. Using Cytohabba, it was found that the genes UBE2N, BRCA1, BARD1, TP53, and DPP4 had a high degree and centrality score. The drugs 5-fluorouracil, Methotrexate, Temozolomide, Favipiravir, and Levofloxacin have a substantial association with the hub protein, according to protein-drug interaction analysis. Finally, a docking study revealed that 5-fluorouracil has the highest connection value and stability compared to Methotrexate, Favipiravir, and Levofloxacin.

Conclusion: The biomolecular networking study was used to discover the link between TP53 and SARS-CoV-2, and it was found that 5-fluorouracil had a higher affinity for binding to TP53 and its related genes, such as UBE2N, BRCA1, RARD1, and SARS-CoV-2 specific DPP4. For cancer patients with TP53 gene mutations and Covid-19 infection, this treatment is determined to be the most effective.

Keywords: TP53 gene, Covid-19, cancer, molecular networking, mutation, anticancer drug.

« Previous
Graphical Abstract

[1]
Addeo A, Friedlaender A. Cancer and COVID-19: Unmasking their ties. Cancer Treat Rev 2020; 88: 102041.
[http://dx.doi.org/10.1016/j.ctrv.2020.102041] [PMID: 32516704]
[2]
Franco P, Kochbati L, Siano M, De Bari B. Suggestions for radiation oncologists during the COVID-19 pandemic. BioMed Res Int 2020; 2020: 4892382.
[http://dx.doi.org/10.1155/2020/4892382] [PMID: 32509860]
[3]
Olivier M, Hollstein M, Hainaut P. TP53 mutation in human cancer: Origins, consequences, and clinical use. Cold spring harbor perspective in biology 2009; 2(1)
[4]
Feroz W, Sheikh A. Exploring the multiple roles of guardian of the genome: P53. Egypt J Med Hum Genet 2020; 21(1)
[5]
Toppgene.cchmc.org. Welcome to ToppGene. 2021. Available at: https://toppgene.cchmc.org/
[6]
Hardcastle I. Protein-Protein interaction inhibitors in Cancer. Comprehensive Medicinal Chemistry 2017; III: 154-201.
[http://dx.doi.org/10.1016/B978-0-12-409547-2.12392-3]
[7]
Krasner J. Drug-protein interaction. Pediatric Clinics of North America 2009; 19(1): 51-63.
[8]
Olivier M, Hollstein M, Hainaut P. TP53 mutations in human cancers: Origins, consequences, and clinical use. Cold Spring Harb Perspect Biol 2010; 2(1): a001008-8.
[http://dx.doi.org/10.1101/cshperspect.a001008] [PMID: 20182602]
[9]
Sousa SF, Fernandes PA, Ramos MJ. Protein-ligand docking: Current status and future challenges. Proteins 2006; 65(1): 15-26.
[http://dx.doi.org/10.1002/prot.21082] [PMID: 16862531]
[10]
Hollingsworth SA, Dror RO. Molecular dynamics simulation for all. Neuron 2018; 99(6): 1129-43.
[http://dx.doi.org/10.1016/j.neuron.2018.08.011] [PMID: 30236283]
[11]
Iyer PM, Karthikeyan S, Sanjay Kumar P, Krishnan Namboori PK. Comprehensive strategy for the design of precision drugs and identification of genetic signature behind proneness of the disease-a pharmacogenomic approach. Funct Integr Genomics 2017; 17(4): 375-85.
[http://dx.doi.org/10.1007/s10142-017-0559-7] [PMID: 28470340]
[12]
Anand C, Vyshnavi A, Francis G, Karthikeyan S, Sanjay Kumar P, Namboori P. Population wise variation of breast and ovarian cancer-a pharmacogenomic approach. Mater Today Proc 2018; 5(8): 16106-10.
[http://dx.doi.org/10.1016/j.matpr.2018.05.094]
[13]
Chen J, Bardes E, Aronow B, Jegga A. ToppGene Suite for gene list enrichment analysis and candidate gene prioritization Nucleic Acids Research 2009; 37(Web Server):W305-11.
[http://dx.doi.org/10.1093/nar/gkp427]
[14]
Ono K. 2021.Cytoscape: An open-source platform for complex network analysis and visualization. Available at: https://cytoscape.org/
[15]
Cytoscape App Store - cytoHubba. 2021. Available at: https://apps.cytoscape.org/apps/cytohubba
[16]
Pyrx.sourceforge.io. 2021.Welcome to the PyRx Website. Available at: https://pyrx.sourceforge.io/
[17]
Bank R. 2021.RCSB PDB: Homepage https://www.rcsb.org/
[18]
Go.drugbank.com. DrugBank Online | Database for drug and drug target info. 2021. Available at: https://go.drugbank.com/
[19]
Ks.uiuc.edu. NAMD - Scalable Molecular Dynamics. 2021. Available at: https://www.ks.uiuc.edu/Research/namd/
[20]
Life.illinois.edu. 2022. Available from: namd-tutorialunix-590C.pdf (illinois.edu). 2022.
[21]
Uniprot.org. UniProt. 2021. Available at: https://www.uniprot.org/

Rights & Permissions Print Cite
Article Metrics
12
1
© 2024 Bentham Science Publishers | Privacy Policy