Ukr.Biochem.J. 2024; Volume 96, Issue 5, Sep-Oct, pp. 119-129
doi: https://doi.org/10.15407/ubj96.05.119
Virtual screening of antiviral peptides as novel blockers of human papillomavirus 16
H. Al-Madhagi
Biochemical Technology Program, Dhamar University, Dhamar, Yemen;
e-mail: bio.haitham@gmail.com
Received: 08 June 2024; Revised: 09 July 2024;
Accepted: 07 October 2024; Available on-line: 28 October 2024
Human papillomaviruses (HPVs) contribute to 5% of cancers, yet there is a lack of specific antiviral agents targeting HPV infection. Antiviral peptides (AVPs) present a promising alternative to conventional therapeutics. This study aims to explore the use of AVPs against the HPV16 E6 oncoprotein through virtual screening. The potential binding pocket of the E6 oncoprotein was determined, and using the antimicrobial CAMPR4 database 18 AVPs were shortlisted. These AVPs were then docked to the E6 oncoprotein using the HawkDock server, followed by dynamic simulation. Among the AVPs tested, AVP18, AVP10, and AVP7 demonstrated the highest inhibitory potential against the E6 oncoprotein. AVP18 exhibited more non-bonded contacts, hydrogen bonds, and electrostatic forces. Dynamics simulation confirmed the stability of the complexes formed by these top AVPs with E6. This research suggests that AVP7, AVP10, and AVP18 are promising lead candidates for blocking HPV16 by inhibiting the E6 oncoprotein.
Keywords: antiviral peptides, docking, dynamics simulation, E6 oncoprotein, human papillomavirus
References:
- Yarbrough ML, Burnham CA. The ABCs of STIs: An Update on Sexually Transmitted Infections. Clin Chem. 2016;62(6):811-823. PubMed, CrossRef
- Chesson HW, Dunne EF, Hariri S, Markowitz LE. The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex Transm Dis. 2014;41(11):660-664. PubMed, PubMedCentral, CrossRef
- Haley CT, Mui UN, Vangipuram R, Rady PL, Tyring SK. Human oncoviruses: Mucocutaneous manifestations, pathogenesis, therapeutics, and prevention: Papillomaviruses and Merkel cell polyomavirus. J Am Acad Dermatol. 2019;81(1):1-21. PubMed, CrossRef
- Buchanan TR, Graybill WS, Pierce JY. Morbidity and mortality of vulvar and vaginal cancers: Impact of 2-, 4-, and 9-valent HPV vaccines. Hum Vaccin Immunother. 2016;12(6):1352-1356. PubMed, PubMedCentral, CrossRef
- de Martel C, Plummer M, Vignat J, Franceschi S. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer. 2017;141(4):664-670. PubMed, PubMedCentral, CrossRef
- Plummer M, de Martel C, Vignat J, Ferlay J, Bray F, Franceschi S. Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Health. 2016;4(9):e609-e616. PubMed, CrossRef
- de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, Tous S, Felix A, Bravo LE, Shin HR, Vallejos CS. et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11(11):1048-1056. PubMed, CrossRef
- Human papillomavirus genomics: past, present and future. Curr Probl Dermatol. 2014:45:1-18. PubMed, PubMedCentral, CrossRef
- Mirabello L, Clarke MA, Nelson CW, Dean M, Wentzensen N, Yeager M, Cullen M, Boland JF, NCI HPV Workshop, Schiffman M, Burk RD. The Intersection of HPV Epidemiology, Genomics and Mechanistic Studies of HPV-Mediated Carcinogenesis. Viruses. 2018;10(2):80. PubMed, PubMedCentral, CrossRef
- Dasgupta J, Bienkowska-Haba M, Ortega ME, Patel HD, Bodevin S, Spillmann D, Bishop B, Sapp M, Chen XS. Structural basis of oligosaccharide receptor recognition by human papillomavirus. J Biol Chem. 2011;286(4):2617-2624. PubMed, PubMedCentral, CrossRef
- Kombe Kombe AJ, Li B, Zahid A, Mengist HM, Bounda GA, Zhou Y, Jin T. Epidemiology and Burden of Human Papillomavirus and Related Diseases, Molecular Pathogenesis, and Vaccine Evaluation. Front Public Health. 2021;8:552028. PubMed, PubMedCentral, CrossRef
- Arbyn M, Xu L, Simoens C, Martin-Hirsch PP. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev. 2018;5(5):CD009069. PubMed, PubMedCentral, CrossRef
- Yu Y, Guo J, Li D, Liu Y, Yu Y, Wang L. Development of a human papillomavirus type 6/11 vaccine candidate for the prevention of condyloma acuminatum. Vaccine. 2018;36(32 Pt B):4927-4934. PubMed, CrossRef
- Chen W, Zhao Y, Xie X, Liu J, Li J, Zhao C, Wang S, Liao X, Shou Q, Zheng M, Saah AJ, Wei L, Qiao Y. Safety of a quadrivalent human papillomavirus vaccine in a Phase 3, randomized, double-blind, placebo-controlled clinical trial among Chinese women during 90 months of follow-up. Vaccine. 2019;37(6):889-897. PubMed, CrossRef
- Patel C, Brotherton JM, Pillsbury A, Jayasinghe S, Donovan B, Macartney K, Marshall H. The impact of 10 years of human papillomavirus (HPV) vaccination in Australia: what additional disease burden will a nonavalent vaccine prevent? Euro Surveill. 2018;23(41):1700737. PubMed, PubMedCentral, CrossRef
- Latsuzbaia A, Arbyn M, Tapp J, Fischer M, Weyers S, Pesch P, Mossong J. Effectiveness of bivalent and quadrivalent human papillomavirus vaccination in Luxembourg. Cancer Epidemiol. 2019;63:101593. PubMed, CrossRef
- Lei J, Ploner A, Elfström KM, Wang J, Roth A, Fang F, Sundström K, Dillner J, Sparén P. HPV Vaccination and the Risk of Invasive Cervical Cancer. N Engl J Med. 2020;383(14):1340-1348. PubMed, cr id=”https://doi.org/10.1056/NEJMoa1917338″]
- Harro CD, Pang YY, Roden RB, Hildesheim A, Wang Z, Reynolds MJ, Mast TC, Robinson R, Murphy BR, Karron RA, Dillner J, Schiller JT, Lowy DR. Safety and immunogenicity trial in adult volunteers of a human papillomavirus 16 L1 virus-like particle vaccine. J Natl Cancer Inst. 2001;93(4):284-292. PubMed, CrossRef
- Jabeen M, Biswas P, Islam MT, Paul R. Antiviral Peptides in Antimicrobial Surface Coatings-From Current Techniques to Potential Applications. Viruses. 2023;15(3):640. PubMed, PubMedCentral, CrossRef
- Essa RZ, Wu YS, Batumalaie K, Sekar M, Poh CL. Antiviral peptides against SARS-CoV-2: therapeutic targets, mechanistic antiviral activity, and efficient delivery. Pharmacol Rep. 2022;74(6):1166-1181. PubMed, PubMedCentral, CrossRef
- Lee YJ, Shirkey JD, Park J, Bisht K, Cowan AJ. An Overview of Antiviral Peptides and Rational Biodesign Considerations. Biodes Res. 2022;2022:9898241. PubMed, PubMedCentral, CrossRef
- Graef J, Ehrt C, Rarey M. Binding Site Detection Remastered: Enabling Fast, Robust, and Reliable Binding Site Detection and Descriptor Calculation with DoGSite3. J Chem Inf Model. 2023;63(10):3128-3137. PubMed, CrossRef
- Gawde U, Chakraborty S, Waghu FH, Barai RS, Khanderkar A, Indraguru R, Shirsat T, Idicula-Thomas S. CAMPR4: a database of natural and synthetic antimicrobial peptides. Nucleic Acids Res. 2023;51(D1):D377-D383. PubMed, PubMedCentral, CrossRef
- Weng G, Wang E, Wang Z, Liu H, Zhu F, Li D, Hou T. HawkDock: a web server to predict and analyze the protein-protein complex based on computational docking and MM/GBSA. Nucleic Acids Res. 2019;47(W1):W322-W330. PubMed, PubMedCentral, CrossRef
- Laskowski RA, Jabłońska J, Pravda L, Vařeková RS, Thornton JM. PDBsum: Structural summaries of PDB entries. Protein Sci. 2018;27(1):129-134. PubMed, PubMedCentral, CrossRef
- Kuriata A, Gierut AM, Oleniecki T, Ciemny MP, Kolinski A, Kurcinski M, Kmiecik S. CABS-flex 2.0: a web server for fast simulations of flexibility of protein structures. Nucleic Acids Res. 2018;46(W1):W338-W343. PubMed, PubMedCentral, CrossRef
- Cubie HA. Diseases associated with human papillomavirus infection. Virology. 2013;445(1-2):21-34. PubMed, CrossRef
- Bruno MT, Cassaro N, Bica F, Boemi S. Progression of CIN1/LSIL HPV Persistent of the Cervix: Actual Progression or CIN3 Coexistence. Infect Dis Obstet Gynecol. 2021;2021:6627531. PubMed, PubMedCentral, CrossRef
- Kamolratanakul S, Pitisuttithum P. Human Papillomavirus Vaccine Efficacy and Effectiveness against Cancer. Vaccines (Basel). 2021;9(12):1413. PubMed, PubMedCentral, CrossRef
- Vilas Boas LCP, Campos ML, Berlanda RLA, de Carvalho Neves N, Franco OL. Antiviral peptides as promising therapeutic drugs. Cell Mol Life Sci. 2019;76(18):3525-3542. PubMed, PubMedCentral, CrossRef
- Loffredo MR, Nencioni L, Mangoni ML, Casciaro B. Antimicrobial peptides for novel antiviral strategies in the current post-COVID-19 pandemic. J Pept Sci. 2024;30(1):e3534. PubMed, CrossRef
- Ashaolu TJ, Nawaz A, Walayat N, Khalifa I. Potential “biopeptidal” therapeutics for severe respiratory syndrome coronaviruses: a review of antiviral peptides, viral mechanisms, and prospective needs. Appl Microbiol Biotechnol. 2021;105(9):3457-3470. PubMed, PubMedCentral, CrossRef
- Mishra J. Potential Antiviral Drug Against Human Papillomavirus Type 16 Through Indandione-Containing Inhibitors of E1-E2 Protein Interaction. ECS Trans. 2022;107(1): 2859. CrossRef
- Mistry N, Drobni P, Näslund J, Sunkari VG, Jenssen H, Evander M. The anti-papillomavirus activity of human and bovine lactoferricin. Antiviral Res. 2007;75(3):258-265. PubMed, CrossRef
- Buck CB, Day PM, Thompson CD, Lubkowski J, Lu W, Lowy DR,Schiller JT. Human alpha-defensins block papillomavirus infection. Proc Natl Acad Sci USA. 2006;103(5):1516-1521. PubMed, PubMedCentral, CrossRef
- Zhang P, Moreno R, Lambert PF, DiMaio D. Cell-penetrating peptide inhibits retromer-mediated human papillomavirus trafficking during virus entry. Proc Natl Acad Sci USA. 2020;117(11):6121-6128. PubMed, PubMedCentral, CrossRef
- Agarwal G, Gabrani R. Antiviral Peptides: Identification and Validation. Int J Pept Res Ther. 2021;27(1):149-168. PubMed, PubMedCentral, CrossRef
- Gao B, Zhao D, Li L, Cheng Z, Guo Y. Antiviral Peptides with in vivo Activity: Development and Modes of Action. Chempluschem. 2021;86(12):1547-1558. PubMed, CrossRef
