New Approach to create an Effective Natural Treatments of Infections caused by Human Papillomavirus
DOI:
https://doi.org/10.33084/jmd.v1i2.3011Keywords:
HPV-16, Cervical carcinoma, Apigenin, Celery, 1-Click Docking, Major capsid protein L1Abstract
Human Papillomavirus (HPV) has a double-stranded DNA (dsDNA) genome. Infections, mainly sexually transmitted, usually resolve spontaneously. However, if the infection persists over time, lesions of the skin and mucous membranes tend to appear, notably mucosal lesions in the cervix or the appearance of warts. Some of those slowly progress to cancers such as cervical, oral, anus, esophagus, and larynx carcinoma. Diagnosis of an HPV infection is made by Papanicolaou test (Pap test) or molecular screening such as the HPV DNA Test. Treatment with natural products is based on essential oils. The main point of this work is to identify natural molecules from vegetal derivation capable of inhibiting the proliferation of HPV-16 with the same and/or superior affinity as regular drugs used in pharmacological treatment. Once we have identified the main components in these plants, we have applied molecular docking software 1-Click Docking, for virtual testing of those, on main antigenic determinants of HPV-16 as oncoproteins E6 and E7 as well as major capsid protein L1. The major active component to bind oncoprotein E6, apigenin, has shown an affinity bigger than other molecules. For major capsid protein L1, apigenin has shown one level of affinity similar to conventional drugs. These results have shown how it is possible, with natural products present in our daily lives, to inhibit the proliferation of HPV.
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References
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33. Dhifi W, Bellili S, Jazi S, Bahloul N, Mnif W. Essential Oils' Chemical Characterization and Investigation of Some Biological Activities: A Critical Review. Medicines. 2016;3(4):25. doi:10.3390/medicines3040025
2. Yoshino M, Nagamatsu A, Tsutsumi K, Kanazawa A. The regulatory function of the upstream sequence of the beta-conglycinin alpha subunit gene in seed-specific transcription is associated with the presence of the RY sequence. Genes Genet Syst. 2006;81(2):135-41. doi:10.1266/ggs.81.135
3. Ferreira AR, Ramalho AC, Marques M, Ribeiro D. The Interplay between Antiviral Signalling and Carcinogenesis in Human Papillomavirus Infections. Cancers. 2020;12(3):646. doi:10.3390/cancers12030646
4. Ibarra AMR, Legendre L, Munday JS. Malignant Transformation of a Canine Papillomavirus Type 1-Induced Persistent Oral Papilloma in a 3-Year-Old Dog. J Vet Dent. 2018;35(2):79-95. doi:10.1177/0898756418774575
5. Mirkovic J, Howitt BE, Roncarati P, Demoulin S, Suarez-Carmona M, Hubert P. Carcinogenic HPV infection in the cervical squamo-columnar junction. J Pathol. 2015;236(6):265-71. doi:10.1002/path.4533
6. Crosbie EJ, Einstein MH, Franceschi S, Kitchener HC. Human papillomavirus and cervical cancer. Lancet. 2013;382(9895):889-99. doi:10.1016/s0140-6736(13)60022-7
7. Gillison ML. Human papillomavirus-related diseases: oropharynx cancers and potential implications for adolescent HPV vaccination. J Adolesc Health. 2008;43(4 Suppl):S52-S60. doi:10.1016/j.jadohealth.2008.07.002
8. Koliopoulos G, Nyaga VN, Santesso N, Bryant A, Martin-Hirsch PP, Mustafa RA, et al. Cytology versus HPV testing for cervical cancer screening in the general population. Cochrane Database Syst Rev. 2017;8(8):CD008587. doi:10.1002/14651858.cd008587.pub2
9. El-Zein M, Richardson L, Franco EL. Cervical cancer screening of HPV vaccinated populations: Cytology, molecular testing, both or none. J Clin Virol. 2016;Suppl 1(Suppl 1):S62-S68. doi:10.1016/j.jcv.2015.11.020
10. Maine D, Hurlburt S, Greeson D. Cervical cancer prevention in the 21st century: cost is not the only issue. Am J Public Health. 2011;101(9):1549-55. doi:10.2105/ajph.2011.300204
11. Lee SM, Park JS, Norwitz ER, Koo JN, Oh IH, Park JW, et al. Risk of vertical transmission of human papillomavirus throughout pregnancy: a prospective study. PLoS One. 2013;8(6):e66368. doi:10.1371/journal.pone.0066368
12. Tuladhar E, Terpstra P, Koopmans M, Duizer E. Virucidal efficacy of hydrogen peroxide vapour disinfection. J Hosp Infect. 2012;80(2):110-5. doi:10.1016/j.jhin.2011.10.012
13. Meyers J, Ryndock E, Conway MJ, Meyers C, Robison R. Susceptibility of high-risk human papillomavirus type 16 to clinical disinfectants. J Antimicrob Chemother. 2014;69(6):1546-50. doi:10.1093/jac/dku006
14. Stern PL, van der Burg SH, Hampson IN, Broker TR, Fiander A, Lacey CJ, et al. Therapy of human papillomavirus-related disease. Vaccine. 2012;30 Suppl 5 (0 5):F71-F82. doi:10.1016/j.vaccine.2012.05.091
15. Fradet-Turcotte A, Archambault J. Recent advances in the search for antiviral agents against human papillomaviruses. Antivir Ther. 2007;12(4):431-51.
16. Miller RL, Gerster JF, Owens ML, Slade HB, Tomai MA. Imiquimod applied topically: a novel immune response modifier and new class of drug. Int J Immunopharmacol. 1999;21(1):1-14. doi:10.1016/s0192-0561(98)00068-x
17. Lipke MM. An armamentarium of wart treatments. Clin Med Res. 2006;4(4):273-93. doi:10.3121/cmr.4.4.273
18. Yanofsky VR, Patel RV, Goldenberg G. Genital warts: a comprehensive review. J Clin Aesthet Dermatol. 2012;5(6):25-36.
19. Das S. Human Papillomavirus Infection: Management and Treatment. London (UK): IntechOpen; 2020. doi:10.5772/intechopen.92397
20. Mutombo AB, Tozin R, Kanyiki H, Geertruyden JPV, Jacquemyn Y. Impact of antiviral AV2 in the topical treatment of HPV-associated lesions of the cervix: Results of a phase III randomized placebo-controlled trial. Contemp Clin Trials Commun. 2019;15:100377. doi:10.1016/j.conctc.2019.100377
21. Dunjic M, Stanisic S, Krstic D, Stanisic M, Ignjatic ZJ, Dunjic M. Integrative approach to diagnosis of genital human papillomaviruses (HPV) infection of female. Acupunct Electrother Res. 2014;39(3-4):229-39. doi:10.3727/036012914x14109544776051
22. Zanier K, Sidi AM, Boulade-Ladame C, Rybin V, Chappelle A, Atkinson A, et al. Solution structure analysis of the HPV16 E6 oncoprotein reveals a self-association mechanism required for E6-mediated degradation of p53. Structure. 2012;20(4):604-17. doi:10.1016/j.str.2012.02.001
23. Facciuto F, Valdano MB, Marziali F, Massimi P, Banks L, Cavatorta AL, et al. Human papillomavirus (HPV)-18 E6 oncoprotein interferes with the epithelial cell polarity Par3 protein. Mol Oncol. 2014;8(3):533-43. doi:10.1016/j.molonc.2014.01.002
24. Saikia S, Bordoloi M. Molecular Docking: Challenges, Advances and its Use in Drug Discovery Perspective. Curr Drug Targets. 2019;20(5):501-21. doi:10.2174/1389450119666181022153016
25. Du X, Li Y, Xia YL, Ai SM, Liang J, Sang P, et al. Insights into Protein-Ligand Interactions: Mechanisms, Models, and Methods. Int J Mol Sci. 2016;17(2):144. doi:10.3390/ijms17020144
26. Robinson PK. Enzymes: principles and biotechnological applications. Essays Biochem. 2015;59:1-41. doi:10.1042/bse0590001
27. Ferreira LG, Dos Santos RN, Oliva G, Andricopulo AD. Molecular docking and structure-based drug design strategies. Molecules. 2015;20(7):13384-421. doi:10.3390/molecules200713384
28. Kolb P, Irwin JJ. Docking screens: right for the right reasons? Curr Top Med Chem. 2009;9(9):755-70. doi:10.2174/156802609789207091
29. Meng XY, Zhang HX, Mezei M, Cui M. Molecular Docking: A powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des. 2011;7(2):146-57. doi:10.2174/157340911795677602
30. Pinzi L, Rastelli G. Molecular Docking: Shifting Paradigms in Drug Discovery. Int J Mol Sci. 2019;20(18):4331. doi:10.3390/ijms20184331
31. Park MS, Gao C, Stern HA. Estimating binding affinities by docking/scoring methods using variable protonation states. Proteins. 2011;79(1):304-14. doi:10.1002/prot.22883
32. Wootten D, Reynolds CA, Smith KJ, Mobarec JC, Furness SGB, Miller LJ, et al. Key interactions by conserved polar amino acids located at the transmembrane helical boundaries in Class B GPCRs modulate activation, effector specificity and biased signalling in the glucagon-like peptide-1 receptor. Biochem Pharmacol. 2016;118:68-87. doi:10.1016/j.bcp.2016.08.015
33. Dhifi W, Bellili S, Jazi S, Bahloul N, Mnif W. Essential Oils' Chemical Characterization and Investigation of Some Biological Activities: A Critical Review. Medicines. 2016;3(4):25. doi:10.3390/medicines3040025
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Published
2021-12-30
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1.
Dunjic M, Turini SG, Stanisic S, Sulovic N, Cvetkovic S, Mihajlovic D, Dunjic M, Simic D, Dunjic K. New Approach to create an Effective Natural Treatments of Infections caused by Human Papillomavirus. J Mol Docking [Internet]. 2021Dec.30 [cited 2024Nov.15];1(2):68-77. Available from: https://journal.umpr.ac.id/index.php/jmd/article/view/3011
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