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Repurposing Pheophorbide a as an Antiviral Molecule for Human Papillomavirus type 16

Yıl 2025, Cilt: 15 Sayı: 2, 745 - 763, 15.06.2025
https://doi.org/10.31466/kfbd.1607109

Öz

The emergence of human papillomavirus (HPV) among the human population in different regions of the world has heightened the interest for new treatment methods. Molecular docking is a reliable and predictive method for screening of new potential antiviral molecules against pathogens. The retrieved 42 high-quality whole-genome sequences of HPV were analyzed in search of a stable region which is exist in the genome. The protein encoded by this stable region was targeted for protein-ligand interaction. Consequently, a target constant region which is responsible for encoding the C-terminal domain (monomer) of the HPV45 oncoprotein E7 (PDB: 2ewl) with various regulatory functions for the virus was detected. A ligand “Pheophorbide a (C35H36N4O5)” interacts with this protein, which could be used against HPV. Pheophorbide a has also been commercially used for cancer treatments due to its anti-proliferative effects and photosensitizer property in photodynamic therapy. This possible antiviral property of Pheophorbide a should be tested on other high-risk and low-risk Papillomaviruses since the E7 oncoprotein also plays a central role in many other HPV types. The predictive results need confirmation with further clinical and in vitro studies. The findings will provide new insights into HPV-human cell interactions, induced immunity, and new methods for HPV treatment.

Etik Beyan

The author declares that this study complies with Research and Publication Ethics.

Destekleyen Kurum

The author received no financial support for the research, authorship, and publication of this article.

Teşekkür

This article is dedicated to HPV patients. The author gratefully thanks to Prof. Dr. Ömür Baysal for his comments and suggestions. The sequence data of this study are openly available in the NCBI database. Supplementary materials are available online: https://doi.org/10.6084/m9.figshare.28028489

Kaynakça

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Feoforbid a'nın İnsan Papilloma Virüsü Tip 16'ya Karşı Kullanımı

Yıl 2025, Cilt: 15 Sayı: 2, 745 - 763, 15.06.2025
https://doi.org/10.31466/kfbd.1607109

Öz

Dünyanın farklı bölgelerindeki insan popülasyonunda insan papillomavirüsünün (HPV) ortaya çıkması, yeni tedavi yöntemlerine olan ilgiyi artırmıştır. Moleküler yerleştirme, patojenlere karşı yeni potansiyel antiviral moleküllerin taranması için güvenilir ve öngörücü bir yöntemdir Yüksek kaliteli 42 HPV tüm genom dizisi, genomda sabit bir bölgenin varlığı açısından analiz edildi. Bu sabit bölge tarafından kodlanan protein, protein-ligand etkileşimi için analiz edildi. Sonuç olarak, virüs bünyesinde çeşitli düzenleyici işlevlere sahip HPV45 oncoprotein E7’nin C-terminal domaini (monomer) (PDB: 2ewl) proteinini kodlamaktan sorumlu bir sabit bölge tespit edildi. HPV'ye karşı kullanılabilecek bir ligand olan "Feoforbid a'nın (C35H36N4O5)" bu proteinle etkileşime girdiği öngörülmüştür. Feoforbid a, fotodinamik terapide anti-proliferatif etkileri ve fotosensitizör özelliği nedeniyle ticari olarak kanser tedavilerinde de kullanılmaktadır. Feoforbid a'nın bu kuvvetle muhtemel antiviral özelliği, E7 onkoproteini birçok farklı HPV tipinde de merkezi bir rol oynadığı için, diğer yüksek riskli ve düşük riskli Papillomavirüsler üzerinde test edilmelidir. Bu sonuçların daha ileri klinik ve in vitro çalışmalar ile doğrulanması gerekmektedir. Bulgular, HPV-insan hücre etkileşimleri, indüklenen bağışıklık ve HPV tedavisinde geliştirilecek yöntemler konusunda yeni fikirler sağlayabilir.

Kaynakça

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  • Riley, R. R., Duensing, S., Brake, T., Münger, K., Lambert, P. F., and Arbeit, J. M. (2003). Dissection of human papillomavirus E6 and E7 function in transgenic mouse models of cervical carcinogenesis. Cancer Research, 63(16), 4862-4871.
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  • Rossi, M., Bettini, C., and Pagano, C. (2011). Bilateral papilledema following human papillomavirus vaccination. Journal of Medical Cases, 2(5), 222-224. https://doi.org/10.4021/jmc256w
  • Saide, A., Lauritano, C., and Ianora, A. (2020). Pheophorbide a: State of the Art. Marine Drugs, 18(5), 257. https://doi.org/10.3390/md18050257
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  • Schüttelkopf, A. W., and Van Aalten, D. M. F. (2004). PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallographica Section D, 60(8), 1355-1363. https://doi.org/10.1107/s0907444904011679
  • Schwede, T., Kopp, J., Guex, N., and Peitsch, M. C. (2003). SWISS-MODEL: An automated protein homology-modeling server. Nucleic Acids Research, 31(13), 3381-3385. https://doi.org/10.1093/nar/gkg520
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  • Slade, B. A., Leidel, L., Vellozzi, C., Woo, E. J., Hua, W., Sutherland, A., Izurieta, H. S., Ball, R., Miller, N., Braun, M. M., Markowitz, L. E., and Iskander, J. (2009). Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. The Journal of the American Medical Association, 302(7), 750-757. https://doi.org/10.1001/jama.2009.1201
  • Sutton, I., Lahoria, R., Tan, I., Clouston, P., and Barnett, M. (2009). CNS demyelination and quadrivalent HPV vaccination. Multiple Sclerosis Journal, 15, 116-119. https://doi.org/10.1177/1352458508096868
  • Syrjänen, S., and Puranen, M. (2000). Human papillomavirus infections in children: the potential role of maternal transmission. Critical Reviews in Oral Biology & Medicine, 11(2), 259-274. https://doi.org/10.1177/10454411000110020801
  • Szczygieł, M., Urbańska, K., Jurecka, P., Stawoska, I., Stochel, G., and Fiedor, L. (2008). Central metal determines pharmacokinetics of chlorophyll-derived xenobiotics. Journal of Medicinal Chemistry, 51(15), 4412-4418. https://doi.org/10.1021/jm7016368
  • Tagauov, Y. D., Abu-Elsaoud, A. M., Abdrassulova, Z. T., Tuleukhanov, S. T., Salybekova, N. N., Tulindinova, G., and Al-Abkal, F. (2023). Improvement of blood parameters of male rats exposed to different injection doses of liquid chlorophyll. Cureus, 15(3), e36044. https://doi.org/10.7759/cureus.36044
  • Thomas, J. T., Hubert, W. G., Ruesch, M. N., and Laimins, L. A. (1999). Human papillomavirus type 31 oncoproteins E6 and E7 are required for the maintenance of episomes during the viral life cycle in normal human keratinocytes. Proceedings of the National Academy of Sciences U. S. A., 96(15), 8449-8454. https://doi.org/10.1073/pnas.96.15.8449
  • Trott, O., and Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455-461. https://doi.org/10.1002/jcc.21334
  • Van Doorslaer, K., Chen, Z., Bernard, H. U., Chan, P. K. S., DeSalle, R., Dillner, J., Forslund, O., Haga, T., McBride, A. A., Villa, L. L., Burk, R. D., and ICTV Report Consortium. (2018). Virus Taxonomy Profile: Papillomaviridae. Journal of General Virology, 99(8), 989-990. https://doi.org/10.1099/jgv.0.001105
  • Villa, L. L., Sichero, L., Rahal, P., Caballero, O., Ferenczy, A., Rohan, T., and Franco, E. L. (2000). Molecular variants of human papillomavirus types 16 and 18 preferentially associated with cervical neoplasia. Journal of General Virology, 81(12), 2959-2968. https://doi.org/10.1099/0022-1317-81-12-2959
  • Wang, K-K., Li, J., Kim, B-J., Lee, J-H., Shin, H-W., Ko, S-H., Lee, W-Y., Lee, C-H., Jung, S. H., and Kim, Y-R. (2014). Photophysical properties of Pheophorbide-a derivatives and their photodynamic therapeutic effects on a tumor cell line in vitro. International Journal of Photoenergy, 2014(1), 793723. https://doi.org/10.1155/2014/793723
  • Wang, R., Pan, W., Jin, L., Huang, W., Li, Y., Wu, D., Gao, C., Ma, D., and Liao, S. (2020). Human papillomavirus vaccine against cervical cancer: Opportunity and challenge. Cancer Letters, 471, 88-102. https://doi.org/10.1016/j.canlet.2019.11.039
  • Ward, D., Thorsen, N. M., Frisch, M., Valentiner-Branth, P., Mølbak, K., and Hviid, A. (2019). A cluster analysis of serious adverse event reports after human papillomavirus (HPV) vaccination in Danish girls and young women, September 2009 to August 2017. Eurosurveillance, 24(19), 1800380. https://doi.org/10.2807/1560-7917.ES.2019.24.19.1800380
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  • WHO. (2022). WHO HPV Vaccine Global Market Study. Retrieved from https://www.who.int/publications/m/item/who-hpv-vaccine-global-market-study-april-2022
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  • Xodo, L. E., Rapozzi, V., Zacchigna, M., Drioli, S., and Zorzet, S. (2012). The chlorophyll catabolite pheophorbide a as a photosensitizer for the photodynamic therapy. Current Medicinal Chemistry, 19(6), 799-807. https://doi.org/10.2174/092986712799034879
  • Xu, C., Zhang, J., Mihai, D. M., and Washington, I. (2014). Light-harvesting chlorophyll pigments enable mammalian mitochondria to capture photonic energy and produce ATP. Journal of Cell Science, 127(2), 388-399. https://doi.org/10.1242/jcs.134262
  • Yamada, T., Manos, M. M., Peto, J., Greer, C. E., Munoz, N., Bosch, F. X., and Wheeler, C. M. (1997). Human papillomavirus type 16 sequence variation in cervical cancers: a worldwide perspective. Journal of Virology, 71(3), 2463-2472. https://doi.org/10.1128/jvi.71.3.2463-2472.1997
  • Yamada, T., Wheeler, C. M., Halpern, A. L., Stewart, A. C., Hildesheim, A., and Jenison, S. A. (1995). Human papillomavirus type 16 variant lineages in United States populations characterized by nucleotide sequence analysis of the E6, L2, and L1 coding segments. Journal of Virology, 69, 7743-7753. https://doi.org/10.1128/jvi.69.12.7743-7753.1995
  • Yang, J., Wang, W., Wang, Z., Wang, Z., Wang, Y., Wang, J., Zhao, W., Li, D., and Liu, H. (2019). Prevalence, genotype distribution and risk factors of cervical HPV infection in Yangqu, China: a population-based survey of 10086 women. Human Vaccines & Immunotherapeutics, 16(7), 1645–1652. https://doi.org/10.1080/21645515.2019.1689743
  • Yang, J., Yan, R., Roy, A., Xu, D., Poisson, J., and Zhang, Y. (2015). The I-TASSER Suite: Protein structure and function prediction. Nature Methods, 12(1), 7-8. https://doi.org/10.1038/nmeth.3213
  • Yoon, H., Oh, S., Kim, S., Yoon, J., and Ahn, S. (2014). Pheophorbide a-mediated photodynamic therapy induces autophagy and apoptosis via the activation of MAPKs in human skin cancer cells. Oncology Reports, 31(1), 137-144. https://doi.org/10.3892/or.2013.2856
  • Zerfass-Thome, K., Zwerschke, W., Mannhardt, B., Tindle, R., Botz, J. W., and Jansen-Durr, P. (1996). Inactivation of the cdk inhibitor p27KIP1 by the human papillomavirus type 16 E7 oncoprotein. Oncogene, 13(11), 2323-2330.
Toplam 94 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Biyomühendislik (Diğer)
Bölüm Makaleler
Yazarlar

Ragıp Soner Silme 0000-0001-6547-3747

Yayımlanma Tarihi 15 Haziran 2025
Gönderilme Tarihi 25 Aralık 2024
Kabul Tarihi 27 Nisan 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 15 Sayı: 2

Kaynak Göster

APA Silme, R. S. (2025). Repurposing Pheophorbide a as an Antiviral Molecule for Human Papillomavirus type 16. Karadeniz Fen Bilimleri Dergisi, 15(2), 745-763. https://doi.org/10.31466/kfbd.1607109