Theoretical studies of phytochemicals with feline infectious peritonitis virus proteins: a search for novel antivirals

Year 2024, Volume: 8 Issue: 2, 460 - 467, 27.06.2024

Barış Kurt

https://doi.org/10.31015/jaefs.2024.2.19

Abstract

Feline Infectious Peritonitis Virus (FIPV) is a highly lethal pathogen affecting cats worldwide. Developing effective antiviral treatments is crucial for managing this disease. This study investigates the potential of flavonoids to act as antiviral agents and allosteric modulators against the FIPV spike protein using molecular docking simulations. Thirteen flavonoids were docked against the FIPV spike protein (PDB ID: 6JX7) in both ligand-free (cleaned) and ligand-bound (uncleaned) states to assess their binding affinities and potential allosteric effects. The docking results revealed that all tested flavonoids exhibited strong binding affinities, with docking scores ranging from -7.9 to -9.6 kcal/mol in the cleaned receptor state. Notably, Hesperidin, Morin, Hesperetin, and Quercetin maintained or even improved their binding affinities in the presence of native ligands, suggesting their potential as allosteric modulators. Comparative analysis of the binding modes in the cleaned and uncleaned receptor states further supports the allosteric modulator potential of Morin, Hesperetin, and Hesperidin. These findings highlight the promising role of flavonoids as antiviral agents and allosteric modulators targeting the FIPV spike protein. Further experimental validation and optimization of these compounds could lead to the development of effective treatments for feline infectious peritonitis. This study provides valuable insights into the application of flavonoids in the management of viral diseases and contributes to the ongoing efforts in antiviral drug discovery.

Keywords

FIPV, Flavonoid, Docking, Allosteric Modulators

References

• Aksono, E. B., Iradatya, K. R., Sucipto, T. H., Fajar, N. S. & Yuniarti, W. M. (2023). Phylogenetic analysis of feline infectious peritonitis virus, feline enteric coronavirus, and severe acute respiratory syndrome coronavirus 2 of cats in Surabaya, Indonesia. Veterinary World, 76–81. https://doi.org/10.14202/vetworld.2023.76-81
• Barua, S., Kaltenboeck, B., Juan, Y.-C., Bird, R. C. & Wang, C. (2023). Comparative Evaluation of GS-441524, Teriflunomide, Ruxolitinib, Molnupiravir, Ritonavir, and Nirmatrelvir for In Vitro Antiviral Activity against Feline Infectious Peritonitis Virus. Veterinary Sciences, 10(8), 513. https://doi.org/10.3390/vetsci10080513 Berman, H. M. (2000). The Protein Data Bank. Nucleic Acids Research, 28(1), 235–242. https://doi.org/10.1093/nar/28.1.235
• BIOVIA. (2019). Discovery Studio Visualizer. Dassault Systèmes.
• Chawla, M., Cuspoca, A. F., Akthar, N., Magdaleno, J. S. L., Rattanabunyong, S., Suwattanasophon, C., Jongkon, N., Choowongkomon, K., Shaikh, A. R., Malik, T. & Cavallo, L. (2023). Immunoinformatics-aided rational design of a multi-epitope vaccine targeting feline infectious peritonitis virus. Frontiers in Veterinary Science, 10. https://doi.org/10.3389/fvets.2023.1280273
• Clapham, P. R. & McKnight, Á. (2002). Cell surface receptors, virus entry and tropism of primate lentiviruses. Journal of General Virology, 83(8), 1809–1829. https://doi.org/10.1099/0022-1317-83-8-1809
• Davies, N. M. & Yáñez, J. A. (Eds.). (2012). FLAVONOID PHARMACOKINETICS. Wiley. https://doi.org/10.1002/9781118468524
• Eastman, P., Swails, J., Chodera, J. D., McGibbon, R. T., Zhao, Y., Beauchamp, K. A., Wang, L.-P., Simmonett, A. C., Harrigan, M. P., Stern, C. D., Wiewiora, R. P., Brooks, B. R. & Pande, V. S. (2017). OpenMM 7: Rapid development of high performance algorithms for molecular dynamics. PLOS Computational Biology, 13(7), e1005659. https://doi.org/10.1371/journal.pcbi.1005659
• Eberhardt, J., Santos-Martins, D., Tillack, A. F. & Forli, S. (2021). AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings. Journal of Chemical Information and Modeling, 61(8), 3891–3898. https://doi.org/10.1021/acs.jcim.1c00203
• Gamil Zeedan, G. S. & Abdalhamed, A. M. (2021). Antiviral Effects of Plant Extracts Used in the Treatment of Important Animal Viral Diseases. World’s Veterinary Journal, 11(4), 521–533. https://doi.org/10.54203/scil.2021.wvj67
• Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). The Cambridge Structural Database. Acta Crystallographica Section B Structural Science, Crystal Engineering and Materials, 72(2), 171–179. https://doi.org/10.1107/S2052520616003954
• Irwin, J. J., Sterling, T., Mysinger, M. M., Bolstad, E. S. & Coleman, R. G. (2012). ZINC: A Free Tool to Discover Chemistry for Biology. Journal of Chemical Information and Modeling, 52(7), 1757–1768. https://doi.org/10.1021/ci3001277
• Jiao, Z., Wang, P., Hu, X., Chen, Y., Xu, J., Zhang, J., Wu, B., Luo, R., Shi, Y. & Peng, G. (2024). Feline infectious peritonitis virus ORF7a is a virulence factor involved in inflammatory pathology in cats. Antiviral Research, 222, 105794. https://doi.org/10.1016/j.antiviral.2024.105794
• Kasprzak, M. M., Erxleben, A. & Ochocki, J. (2015). Properties and applications of flavonoid metal complexes. RSC Advances, 5(57), 45853–45877. https://doi.org/10.1039/C5RA05069C
• Markwell, M. A., Portner, A. & Schwartz, A. L. (1985). An alternative route of infection for viruses: entry by means of the asialoglycoprotein receptor of a Sendai virus mutant lacking its attachment protein. Proceedings of the National Academy of Sciences, 82(4), 978–982. https://doi.org/10.1073/pnas.82.4.978
• Meshram, R. J. & Gacche, R. N. (2015). Effective epitope identification employing phylogenetic, mutational variability, sequence entropy, and correlated mutation analysis targeting NS5B protein of hepatitis C virus: from bioinformatics to therapeutics. Journal of Molecular Recognition, 28(8), 492–505. https://doi.org/10.1002/jmr.2466
• Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S. & Olson, A. J. (2009). AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 30(16), 2785–2791. https://doi.org/10.1002/jcc.21256
• Nishijıma, R., Endo, T., Gankhuyag, E., Khın, S. T. M. M., Jafar, S. M., Shinohara, Y., Tanaka, Y., Sawakamı, K., Yohda, M. & Furuya, T. (2023). Detection of anti-feline infectious peritonitis virus activity of a Chinese herb extract using geneLEAD VIII, a fully automated nucleic acid extraction/quantitative PCR testing system. Journal of Veterinary Medical Science, 85(4), 22–0185. https://doi.org/10.1292/jvms.22-0185
• Olotu, F. A., Omolabi, K. F. & Soliman, M. E. S. (2020). Leaving no stone unturned: Allosteric targeting of SARS-CoV-2 spike protein at putative druggable sites disrupts human angiotensin-converting enzyme interactions at the receptor binding domain. Informatics in Medicine Unlocked, 21, 100451. https://doi.org/10.1016/j.imu.2020.100451
• Paredes, A., Alzuru, M., Mendez, J. & Rodríguez-Ortega, M. (2003). Anti-Sindbis Activity of Flavanones Hesperetin and Naringenin. Biological and Pharmaceutical Bulletin, 26(1), 108–109. https://doi.org/10.1248/bpb.26.108
• Pence, H. E. & Williams, A. (2010). ChemSpider: An Online Chemical Information Resource. Journal of Chemical Education, 87(11), 1123–1124. https://doi.org/10.1021/ed100697w
• Sameh A Rizk1, MohyEldin A Abdel-Atti, A. E. A.-R. (2018). Regio-Selective Reaction, Spectroscopic Characterization and Computational Chemical Study of (Hesperidin) Hesperetin-7-O-Rutinoside Analogs as Antimicrobial Agents. Journal of Chemistry: Education Research and Practice, 2(1). https://doi.org/10.33140/JCERP.02.01.13
• Triratapiban, C., Lueangaramkul, V., Phecharat, N., Pantanam, A., Lekcharoensuk, P. & Theerawatanasirikul, S. (2023). First study on in vitro antiviral and virucidal effects of flavonoids against feline infectious peritonitis virus at the early stage of infection. Veterinary World, 618–630. https://doi.org/10.14202/vetworld.2023.618-630
• Wang, J., Wolf, R. M., Caldwell, J. W., Kollman, P. A. & Case, D. A. (2004). Development and testing of a general amber force field. Journal of Computational Chemistry, 25(9), 1157–1174. https://doi.org/10.1002/jcc.20035
• Xue, Q., Liu, X., Russell, P., Li, J., Pan, W., Fu, J., Zhang, A., 2022. Evaluation of the binding performance of flavonoids to estrogen receptor alpha by Autodock, Autodock Vina and Surflex-Dock. Ecotoxicol. Environ. Saf. 233, 113323. https://doi.org/10.1016/j.ecoenv.2022.113323