In silico Screening of the Potential Anti-SARS-CoV-2 Activities of Peptides from Vipera ammodytes ammodytes Venom by Molecular Docking

Öz

The coronavirus disease 2019 (COVID-19) is induced by the SARS-CoV-2 virus, which caused the global pandemic, infecting approximately 608.328.548 confirmed cases and bringing about 6.501.469 deaths worldwide, as WHO stated in September 2022. The disease is more deadly due to the lack of specific drug molecules or a treatment plan. Therefore, the development of potent pharmacological compounds is urgently required to combat COVID-19. Due to their biological actions, snake venoms constitute a source of potentially beneficial medicinal compounds. Vipera ammodytes ammodytes (VA) is a viper species whose venom has been shown to have anti-proliferative, antimetastatic, anti-cancer, and anti-microbial activities. This in silico study was conducted to evaluate the efficacy of selected VA venom proteins (Adamalysin II, Ammodytoxin A, Ammodytin L, L-amino acid oxidase) against molecular targets; Main protease (3CLpro) and Angiotensin-Converting Enzyme 2 (ACE2) by molecular docking study. Molecular docking investigations were performed by using AutoDock Vina software. All compounds displayed negative binding energy values to 3CLpro and ACE2, suggesting that their interactions with the active sites were favourable. L-amino acid oxidase had the highest binding affinity with both 3CLpro and ACE2. This study revealed for the first time that VA venom proteins are functional inhibitors of 3CLpro and ACE2 activities, and the components of VA venom can be considered potential SARS-CoV-2 inhibitors. However, more studies are needed to validate these compounds in vitro and in vivo.

Anahtar Kelimeler

• Vipera ammodytes ammodytes
• SARS-CoV-2
• molecular docking
• venom
• ACE2
• 3CLpro

Kaynakça

1. Ahmad, I., Pawara, R., Surana, S., & Patel, H. (2021). The Repurposed ACE2 Inhibitors: SARS-CoV-2 Entry Blockers of Covid-19. In Topics in Current Chemistry (Vol. 379, Issue 6). https://doi.org/10.1007/s41061-021-00353-7
2. Borkow, G., & Ovadia, M. (1999). Selective lysis of virus-infected cells by cobra snake cytotoxins: A Sendai virus, human erythrocytes, and cytotoxin model. Biochemical and Biophysical Research Communications, 264(1). https://doi.org/10.1006/bbrc.1999.1483
3. El-Aziz, T. M. A., Soares, A. G., & Stockand, J. D. (2019). Snake venoms in drug discovery: Valuable therapeutic tools for life-saving. In Toxins (Vol. 11, Issue 10). https://doi.org/10.3390/toxins11100564
4. Feng, T., Tong, H., Ming, Z., Deng, L., Liu, J., Wu, J., Chen, Z., Yan, Y., & Dai, J. (2022). Matrix metalloproteinase 3 restricts viral infection by enhancing host antiviral immunity. Antiviral Research, 206, 105388. https://doi.org/10.1016/J.ANTIVIRAL.2022.105388
5. Göçmen, B., Heiss, P., Petras, D., Nalbantsoy, A., & Süssmuth, R. D. (2015). Mass spectrometry guided venom profiling and bioactivity screening of the Anatolian Meadow Viper, Vipera anatolica. Toxicon, 107. https://doi.org/10.1016/j.toxicon.2015.09.013
6. Gomis-Ruth, F. X., Kress, L. F., & Bode, W. (1993). First structure of a snake venom metalloproteinase: A prototype for matrix metalloproteinases/collagenases. EMBO Journal, 12(11). https://doi.org/10.1002/j.1460-2075.1993.tb06099.x
7. Gopcevic, K., Karadzic, I., Izrael-Zivkovic, L., Medic, A., Isakovic, A., Popović, M., Kekic, D., Stanojkovic, T., Hozic, A., & Cindric, M. (2021). Study of the venom proteome of Vipera ammodytes ammodytes (Linnaeus, 1758): A qualitative overview, biochemical and biological profiling. Comparative Biochemistry and Physiology Part D: Genomics and Proteomics, 37, 100776. https://doi.org/10.1016/j.cbd.2020.100776
8. Jin, Z., Du, X., Xu, Y., Deng, Y., Liu, M., Zhao, Y., Zhang, B., Li, X., Zhang, L., Peng, C., Duan, Y., Yu, J., Wang, L., Yang, K., Liu, F., Jiang, R., Yang, X., You, T., Liu, X., … Yang, H. (2020). Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature, 582(7811). https://doi.org/10.1038/s41586-020-2223-y

9. Joshi, T., Joshi, T., Sharma, P., Mathpal, S., Pundir, H., Bhatt, V., & Chandra, S. (2020). In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking. European Review for Medical and Pharmacological Sciences, 24(8). https://doi.org/10.26355/eurrev_202004_21036
10. Karabuva, S., Lukšić, B., Brizić, I., Latinović, Z., Leonardi, A., & Križaj, I. (2017). Ammodytin L is the main cardiotoxic component of the Vipera ammodytes ammodytes venom. Toxicon, 139. https://doi.org/10.1016/j.toxicon.2017.10.003
11. Kasai, K., Nakano, M., Ohishi, M., Nakamura, T., & Miura, T. (2021). Antimicrobial properties of L-amino acid oxidase: biochemical features and biomedical applications. In Applied Microbiology and Biotechnology (Vol. 105, Issue 12). https://doi.org/10.1007/s00253-021-11381-0
12. Križaj, I., Bieber, A. L., Ritonja, A., & Gubenšek, F. (1991). The primary structure of ammodytin L, a myotoxic phospholipase A2 homologue from Vipera ammodytes venom. European Journal of Biochemistry, 202(3). https://doi.org/10.1111/j.1432-1033.1991.tb16485.x
13. Latinović, Z., Leonardi, A., Šribar, J., Sajevic, T., Žužek, M. C., Frangež, R., Halassy, B., Trampuš-Bakija, A., Pungerčar, J., & Križaj, I. (2016). Venomics of Vipera berus berus to explain differences in pathology elicited by Vipera ammodytes ammodytes envenomation: Therapeutic implications. Journal of Proteomics, 146. https://doi.org/10.1016/j.jprot.2016.06.020
14. Logonder, U., Križaj, I., Rowan, E. G., & Harris, J. B. (2008). Neurotoxicity of ammodytoxin A in the envenoming bites of Vipera ammodytes ammodytes. Journal of Neuropathology and Experimental Neurology, 67(10). https://doi.org/10.1097/NEN.0b013e318188c2d7
15. Meenakshisundaram, R., Sweni, S., & Thirumalaikolundusubramanian, P. (2009). Hypothesis of snake and insect venoms against Human Immunodeficiency Virus: A review. In AIDS Research and Therapy (Vol. 6). https://doi.org/10.1186/1742-6405-6-25
16. Nalbantsoy, A., Hempel, B.-F., Petras, D., Heiss, P., Göçmen, B., Iğci, N., Yildiz, M. Z., & Süssmuth, R. D. (2017). Combined venom profiling and cytotoxicity screening of the Radde’s mountain viper (Montivipera raddei) and Mount Bulgar Viper (Montivipera bulgardaghica) with potent cytotoxicity against human A549 lung carcinoma cells. Toxicon, 135, 71–83. https://doi.org/10.1016/j.toxicon.2017.06.008
17. Pinzi, L., & Rastelli, G. (2019). Molecular docking: Shifting paradigms in drug discovery. In International Journal of Molecular Sciences (Vol. 20, Issue 18). https://doi.org/10.3390/ijms20184331
18. Pražnikar, Z. J., Petan, T., & Pungerčar, J. (2009). A neurotoxic secretory phospholipase A2 induces apoptosis in motoneuron-like cells. Annals of the New York Academy of Sciences, 1152. https://doi.org/10.1111/j.1749-6632.2008.03999.x
19. Salmaso, V., & Moro, S. (2018). Bridging molecular docking to molecular dynamics in exploring ligand-protein recognition process: An overview. In Frontiers in Pharmacology (Vol. 9, Issue AUG). https://doi.org/10.3389/fphar.2018.00923
20. Sant’Ana, C. D., Menaldo, D. L., Costa, T. R., Godoy, H., Muller, V. D. M., Aquino, V. H., Albuquerque, S., Sampaio, S. V., Monteiro, M. C., Stábeli, R. G., & Soares, A. M. (2008). Antiviral and antiparasite properties of an l-amino acid oxidase from the Snake Bothrops jararaca: Cloning and identification of a complete cDNA sequence. Biochemical Pharmacology, 76(2). https://doi.org/10.1016/j.bcp.2008.05.003
21. Sheahan, T. P., Sims, A. C., Zhou, S., Graham, R. L., Pruijssers, A. J., Agostini, M. L., Leist, S. R., Schafer, A., Dinnon, K. H., Stevens, L. J., Chappell, J. D., Lu, X., Hughes, T. M., George, A. S., Hill, C. S., Montgomery, S. A., Brown, A. J., Bluemling, G. R., Natchus, M. G., … Baric, R. S. (2020). An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Science Translational Medicine, 12(541). https://doi.org/10.1126/SCITRANSLMED.ABB5883
22. Shimizu, J. F., Pereira, C. M., Bittar, C., Batista, M. N., Campos, G. R. F., Da Silva, S., Cintra, A. C. O., Zothner, C., Harris, M., Sampaio, S. V., Aquino, V. H., Rahal, P., & Jardim, A. C. G. (2017). Multiple effects of toxins isolated from Crotalus durissus terrificus on the hepatitis C virus life cycle. PLoS ONE, 12(11). https://doi.org/10.1371/journal.pone.0187857
23. Simon, L., Imane, A., Srinivasan, K. K., Pathak, L., & Daoud, I. (2017). In Silico Drug-Designing Studies on Flavanoids as Anticolon Cancer Agents: Pharmacophore Mapping, Molecular Docking, and Monte Carlo Method-Based QSAR Modeling. Interdisciplinary Sciences – Computational Life Sciences, 9(3). https://doi.org/10.1007/s12539-016-0169-4
24. Siniavin, A. E., Streltsova, M. A., Nikiforova, M. A., Kudryavtsev, D. S., Grinkina, S. D., Gushchin, V. A., Mozhaeva, V. A., Starkov, V. G., Osipov, A. V., Lummis, S. C. R., Tsetlin, V. I., & Utkin, Y. N. (2021). Snake venom phospholipase A2s exhibit strong virucidal activity against SARS-CoV-2 and inhibit the viral spike glycoprotein interaction with ACE2. Cellular and Molecular Life Sciences, 78(23). https://doi.org/10.1007/s00018-021-03985-6
25. Waheed, H., Moin, S. F., & Choudhary, M. I. (2017). Snake Venom: From Deadly Toxins to Life-saving Therapeutics. Current Medicinal Chemistry, 24(17). https://doi.org/10.2174/0929867324666170605091546
26. Wei, J. F., Yang, H. W., Wei, X. L., Qiao, L. Y., Wang, W. Y., & He, S. H. (2009). Purification, characterization and biological activities of the l-amino acid oxidase from Bungarus fasciatus snake venom. Toxicon, 54(3). https://doi.org/10.1016/j.toxicon.2009.04.017
27. Zumla, A., Chan, J. F. W., Azhar, E. I., Hui, D. S. C., & Yuen, K. Y. (2016). Coronaviruses-drug discovery and therapeutic options. In Nature Reviews Drug Discovery (Vol. 15, Issue 5). https://doi.org/10.1038/nrd.2015.37