IN SILICO INVESTIGATION OF ECHINACEA PURPUREA PHYTO LIGANDS TARGETING HUMAN PAPILLOMAVIRUS TYPE 18’S L1 PROTEIN: IMPLICATIONS FOR CERVICAL CANCER MANAGEMENT
DOI:
https://doi.org/10.22159/ijms.2024.v12i3.50778Keywords:
Bioinformatics, HPV infection, HPV type 18, HPV type 16, 2R5I, 2R5H, Cervical Cancer, Molecular Docking, Computational analysisAbstract
Objectives: Human papillomavirus (HPV) is a highly oncogenic virus responsible for the majority of intraepithelial lesions and cervical cancer. Among various HPV types, 16 and 18 contribute to approximately 70% of cervical cancer cases globally, making them the most prevalent high-risk oncogenic variants associated with this disease. Numerous vaccines (Gardasil 9, Gardasil, and Cervarix) have been approved by FDA to combat HPV infections; however, their widespread implementation faces challenges due to their limited cost-effectiveness.
Methods: Echinacea purpurea’s components have already been studied for in silico analysis against HPV Type 16’s L1 protein. In the present analysis, we aimed to explore the potential interaction between E. purpurea phytoligands (curcumin, echinacoside, and chicoric acid) and the major capsid protein L1 of HPV type 18 (2R5I) through molecular docking analysis.
Results: Molecular docking analysis revealed that the echinacoside, one of the components of E. purpurea, has the best binding affinity (−7.9 kcaL/moL) against the L1 protein of the HPV type 18.
Conclusion: The molecular docking analysis indicates that E. purpurea could act as an inhibitor against HPV infection. Further research and in vivo studies are necessary to confirm its efficacy as a cost-effective alternative to present HPV vaccines.
References
Chen AA, Gheit T, Franceschi S, Tommasino M, Clifford GM. Human papillomavirus 18 genetic variation and cervical cancer risk worldwide. J Virol 2015;89:10680-7.
Ahmed HG, Bensumaidea SH, Alshammari FD, Alenazi FS, ALmutlaq BA, Alturkstani MZ, et al. Prevalence of human papillomavirus subtypes 16 and 18 among Yemeni patients with cervical cancer. Asian Pac J Cancer Prev 2017;18:1543-8.
Temesgen MM, Alemu T, Shiferaw B, Legesse S, Zeru T, Haile M, et al. Prevalence of oncogenic human papillomavirus (HPV 16/18) infection, cervical lesions and its associated factors among women aged 21-49 years in Amhara region, Northern Ethiopia. PLoS One 2021;16:e0248949. 4. Wang X, Liu H, Ge H, Ajiro M, Sharma NR, Meyers C, et al. Viral DNA replication orientation and hnRNPs regulate transcription of the human papillomavirus 18 late promoter. mBio 2017;8:e00713-17. 5. Lukman Y, Bala DA, Malik KI, Saidu A, Saleh KA, Abubakar BJ, et al. Identification of HPV16’s E6 gene in suspected cases of cervical lesions and docking study of its L1 protein with active components of Echinacea purpurea. Afr Health Sci 2022;22:98-105.
Ozbun MA. Extracellular events impacting human papillomavirus infections: Epithelial wounding to cell signaling involved in virus entry. Papillomavirus Res 2019;7:188-92.
Barrett B. Medicinal properties of Echinacea: A critical review. Phytomedicine 2003;10:66-86.
Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017;7:42717.
Burley SK, Berman HM, Kleywegt GJ, Markley JL, Nakamura H, Velankar S. Protein Data Bank (PDB): The single global macromolecular structure archive. Methods Mol Biol 2017;1607:627-41.
Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem 2004;25:1605-12.
Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem 2009;30:2785-91.
Yang H, Lou C, Sun L, Li J, Cai Y, Wang Z, et al. admetSAR 2.0: Web-service for prediction and optimization of chemical ADMET properties. Bioinformatics 2019;35:1067-9.
Jabir NR, Rehman MT, Alsolami K, Shakil S, Zughaibi TA, Alserihi RF, et al. Concatenation of molecular docking and molecular simulation of BACE-1, γ-secretase targeted ligands: In pursuit of Alzheimer’s treatment. Ann Med 2021;53:2332-44.
Hernandez J, Elahi A, Siegel E, Coppola D, Riggs B, Shibata D. HPV L1 capsid protein detection and progression of anal squamous neoplasia. Am J Clin Pathol 2011;135:436-41.
King AJ, Sonsma JA, Vriend HJ, van der Sande MA, Feltkamp MC, Boot HJ, et al. genetic diversity in the major capsid L1 protein of HPV- 16 and HPV-18 in the Netherlands. PLoS One 2016;11:e0152782.
Hofmann KJ, Neeper MP, Markus HZ, Brown DR, Müller M, Jansen KU. Sequence conservation within the major capsid protein of human papillomavirus (HPV) type 18 and formation of HPV-18 virus-like particles in Saccharomyces cerevisiae. J Gen Virol 1996;77:465-8.
Published
How to Cite
Issue
Section
Copyright (c) 2024 Vinaya Shinde, Sakshi Chaudhary , Parminder Kaur, Swati Bankariya
This work is licensed under a Creative Commons Attribution 4.0 International License.
