Volume 21, Issue 5 (10-2018)
J Arak Uni Med Sci 2018, 21(5): 7-20 |
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1- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
2- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. , kmansouri@kums.ac.ir
2- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. , kmansouri@kums.ac.ir
Abstract: (2797 Views)
Background and Aim: Human papillomavirus (HPV) infection is a prevalent, life-threatening disease and cause of cancer among women. Therefore, in recent years, developing novel anti-HPV agents is highly regarded. The study was planned to bioinformatic screening for E1 and E2 potential inhibitors of HPV serotypes including 16,18,31,33 and 45 types from medicinal plants.
Materials and Methods: This is a descriptive-analytic study. In the first step, three-dimension structure of phytochemicals were retrieved from PubChem database and then the cell cytotoxicity and mutagenesis potential of them were evaluated. In the next step, the amino acid sequences of two key proteins of mentioned types of HPV including E1 and E2 were obtained from Uniprot database. Furthermore, the conserved and variable regions of the protein sequences were predicted using multiple sequence alignment method. Finally, the three-dimension structure of mentioned proteins was determined by homology modeling method and potential interactions of the phytochemicals with the proteins were investigated using molecular docking method through Autodock 4.2.6 software.
Findings: The results demonstrated that ursolic acid has no cytotoxicity and mutagenesis potential with appropriate physicochemical properties. Results also showed that mentioned compound had strong interaction with both E1 and E2 of all studied serotypes. Furthermore, the evaluation of ursolic acid and E1 and E2 interactions showed that amino acid is involved in conserved regions of mentioned serotypes.
Conclusion: Based on the obtained results of present study ursolic acid could be good candidate for more in vitro and in vivo studies of its anti HPV activity.
Materials and Methods: This is a descriptive-analytic study. In the first step, three-dimension structure of phytochemicals were retrieved from PubChem database and then the cell cytotoxicity and mutagenesis potential of them were evaluated. In the next step, the amino acid sequences of two key proteins of mentioned types of HPV including E1 and E2 were obtained from Uniprot database. Furthermore, the conserved and variable regions of the protein sequences were predicted using multiple sequence alignment method. Finally, the three-dimension structure of mentioned proteins was determined by homology modeling method and potential interactions of the phytochemicals with the proteins were investigated using molecular docking method through Autodock 4.2.6 software.
Findings: The results demonstrated that ursolic acid has no cytotoxicity and mutagenesis potential with appropriate physicochemical properties. Results also showed that mentioned compound had strong interaction with both E1 and E2 of all studied serotypes. Furthermore, the evaluation of ursolic acid and E1 and E2 interactions showed that amino acid is involved in conserved regions of mentioned serotypes.
Conclusion: Based on the obtained results of present study ursolic acid could be good candidate for more in vitro and in vivo studies of its anti HPV activity.
References
1. Morshed, K., et al., Human Papillomavirus (HPV)–Structure, epidemiology and pathogenesis. Otolaryngologia Polska. 2014; 68(5): 213-219.
2. Muñoz, N., et al., Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003; 2003(348): 518-527.
3. Munoz, N., et al., HPV in the etiology of human cancer. Vaccine. 2006; 24: S1-S10.
4. Ferlay, J., et al., Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. International journal of cancer. 2010; 127(12): 2893-2917.
5. Dunne, E.F., et al., Prevalence of HPV infection among females in the United States. Jama. 2007; 297(8): 813-819.
6. Toots, M., et al., Identification of several high-risk HPV inhibitors and drug targets with a novel high-throughput screening assay. PLoS pathogens. 2017; 13(2): e1006168.
7. Faucher, A.-M., et al., Discovery of small-molecule inhibitors of the ATPase activity of human papillomavirus E1 helicase. Journal of medicinal chemistry. 2004; 47(1): 18-21.
8. White, P.W., et al., Biphenylsulfonacetic acid inhibitors of the human papillomavirus type 6 E1 helicase inhibit ATP hydrolysis by an allosteric mechanism involving tyrosine 486. Antimicrobial agents and chemotherapy. 2005; 49(12): 4834-4842.
9. Frattini, M.G. and L.A. Laimins, The role of the E1 and E2 proteins in the replication of human papillomavirus type 31b. Virology. 1994; 204(2): 799-804.
10. Martin, K.W. and E. Ernst, Antiviral agents from plants and herbs: a systematic review. Focus on Alternative and Complementary Therapies. 2003; 8(1): 152-152.
11. Bibi, Y., et al., Antibacterial activity of some selected medicinal plants of Pakistan. BMC complementary and alternative medicine. 2011; 11(1): 52.
12. Madhuri, S. and G. Pandey, Some anticancer medicinal plants of foreign origin. Current science. 2009; 779-783.
13. Nosrati, M. and M. Behbahani, In Vitro and in Silico Evaluation of Antibacterial Effect of Methanolic Extracts of Prangos Ferulacea on Single and Biofilm Structure of Streptococcus Mutans. SSU_Journals. 2016; 23(11): 1049-1062.
14. Yu, W. and A.D. MacKerell, Computer-Aided Drug Design Methods, in Antibiotics. 2017; Springer. 85-106.
15. Balunas, M.J. and A.D. Kinghorn, Drug discovery from medicinal plants. Life sciences. 2005; 78(5): 431-441.
16. Nosrati, M. and M. Behbahani, Molecular Docking Study of HIV-1 Protease with Triterpenoides Compounds from Plants and Mushroom. Arak Uni Med Sci J. 2015; 18(3): 67-79.
17. Nosrati M, Shakeran Z, Shakeran Z. In Silico Screening Hepatitis B Virus DNA Polymerase Inhibitors from Medicinal Plants. Majallah-i dānishgāh-i ̒ulūm-i pizishkī-i Arāk. 2017; 20(5):89-102.
18. Byler, K.G., I.V. Ogungbe, and W.N. Setzer, In-silico screening for anti-Zika virus phytochemicals. Journal of Molecular Graphics and Modelling. 2016; 69: 78-91.
19. Mirza, S.B., et al., Virtual screening of eighteen million compounds against dengue virus: Combined molecular docking and molecular dynamics simulations study. Journal of Molecular Graphics and Modelling. 2016; 66: 99-107.
20. Kumar, S., et al., Virtual screening for potential inhibitors of high-risk human papillomavirus 16 E6 protein. Interdisciplinary Sciences: Computational Life Sciences. 2015; 7(2): 136-142.
21. Griffiths PD, Boeckh M. Antiviral therapy for human cytomegalovirus. In: Arvin A, Campadelli-Fiume G, Mocarski E, et al., editors. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge: Cambridge University Press; 2007. Chapter 66, 1-21.
22. Kapetanovic, I., Computer-aided drug discovery and development (CADDD): in silico-chemico-biological approach. Chemico-biological interactions. 2008; 171(2): 165-176.
23. Nosrati, M., Z. Shakeran, and Z. Shakeran, Frangulosid as a novel hepatitis B virus DNA polymerase inhibitor: a virtual screening study. In Silico Pharmacology. 2018; 6(1): 10.
24. Tambunan, U.S.F., et al., Computational design of drug candidates for influenza A virus subtype H1N1 by inhibiting the viral neuraminidase-1 enzyme. Acta Pharmaceutica. 2014; 64(2): 157-172.
25. Santos, L.H., R.S. Ferreira, and E.R. Caffarena, Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors. Memórias do Instituto Oswaldo Cruz. 2015; 110(7): 847-864.
26. Virupakshaiah, D., et al. Computer Aided Docking Studies on Antiviral Drugs for SARS. in Proceedings of world academy of science, engineering and technology. 2007; 24: 307-6884.
27. Rasheed, U., et al., ADME/T Prediction, Molecular Docking, and Biological Screening of 1, 2, 4-Triazoles as Potential Antifungal Agents. Journal of Applied Bioinformatics & Computational Biology. 2018; 2018.
28. Chiang, L.C., et al., Antiviral activities of extracts and selected pure constituents of Ocimum basilicum. Clinical and Experimental Pharmacology and Physiology. 2005; 32(10): 811-816.
29. Kazakova, O.B., et al., Betulin and ursolic acid synthetic derivatives as inhibitors of Papilloma virus. Bioorganic & medicinal chemistry letters. 2010; 20(14): 4088-4090.
30. Zhao, J., et al., Anti-viral effects of urosolic acid on guinea pig cytomegalovirus in vitro. Journal of Huazhong University of Science and Technology [Medical Sciences]. 2012; 32(6): 883-887.
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