Venom Peptides of Crotalus atrox Against SARS-Cov-2 Spike Protein and Human ACE2 Receptor by Molecular Docking Analysis

Year 2023, Volume: 27 Issue: 4, 735 - 743, 25.08.2023

Süleyman İlhan

https://doi.org/10.16984/saufenbilder.1265332

Abstract

Venoms are composed of about 100 to 500 pharmacologically active compounds. Less than 0.01% of these compounds have been identified and a significant majority of them act on unknown receptors. Here, the potential Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) activities of selected Crotalus atrox venom peptides (CVPs) including Atrolysin D (AD), vascular apoptosis-inducing protein-1 (VAIP-1), Catrocollastatin (CC), and Calcium-Free Phospholipase A2 (CFP) were investigated via molecular docking analysis. CVPs were docked against human angiotensin-converting enzyme-2 (ACE-2) and 3-chymotrypsin-like protease (3CLpro) viral spike protein. All CVPs had low binding energies to both 3CLpro and ACE2, suggesting that they interacted strongly with the active sites of enzymes, compared to the reference drugs lopinavir and ritonavir. The binding energy of 3CLpro was -139.517 kcal/mol, -96.239 kcal/mol, -121.590 kcal/mol, -259.424 kcal/mol with AD, VAIP-1, CC, and CFP, respectively. CFP showed a very strong binding activity with 3CLpro, suggesting that it could be a very effective compound in inhibiting the SARS-CoV-2 virus. The binding energy of ACE2 was -101.165 kcal/mol, -73.064 kcal/mol, -106.918 kcal/mol, -82.830 kcal/mol with AD, VAIP-1, CC, and CFP, respectively. AD made a much stronger bond with ACE2 than reference drugs, showing that it could be used as a virus-protective component in humans. The results suggest a potential drug candidate for the development of therapeutics against Coronavirus disease 2019 (COVID-19). In vitro and in vivo experiments are needed to confirm these compounds' potential preventive and therapeutic effects.

Keywords

Crotalus atrox venom, COVID-19, SARS-CoV-2, 3CLpro, ACE-2.

References

• T. P. Sheahan, Sims, A. C., Zhou, S., Graham, R. L., Pruijssers, A. J., Agostini, M. L., Baric, R. S., “An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice,” Science translational medicine, vol. 12, no. 541, 2020.
• I. Ahmad, R. Pawara, S. Surana, H. Patel, “The Repurposed ACE2 Inhibitors: SARS-CoV-2 Entry Blockers of Covid-19,” Topics in Current Chemistry, vol. 379, no. 6. 2021.
• J. Shang Wan, Y., Luo, C., Ye, G., Geng, Q., Auerbach, A., Li, F., “Cell entry mechanisms of SARS-CoV-2,” Proceedings of the National Academy of Sciences, vol. 117, no. 21, 2020.
• C. B. Jackson, M. Farzan, B. Chen, H. Choe, “Mechanisms of SARS-CoV-2 entry into cells,” Nature Reviews Molecular Cell Biology, vol. 23, no. 1. 2022.
• A. A. Alqathama, Ahmad, R., Alsaedi, R. B., Alghamdi, R. A., Abkar, E. H., Alrehaly, R. H., Abdalla, A. N., “The vital role of animal, marine, and microbial natural products against COVID-19,” Pharmaceutical Biology, vol. 60, no. 1. 2022.
• T. Joshi, Joshi, T., Sharma, P., Mathpal, S., Pundir, H., Bhatt, V., Chandra, S., “In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking,” European Review for Medical and Pharmacological Sciences, vol. 24, no. 8, 2020.
• A. D. Fuzimoto, C. Isidoro, “The antiviral and coronavirus-host protein pathways inhibiting properties of herbs and natural compounds - Additional weapons in the fight against the COVID-19 pandemic?,” Journal of Traditional and Complementary Medicine, vol. 10, no. 4. 2020.
• A. E. Siniavin, Streltsova, M. A., Nikiforova, M. A., Kudryavtsev, D. S., Grinkina, S. D., Gushchin, V. A., Utkin, Y. N., “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, vol. 78, no. 23, 2021.
• T. M. A. El-Aziz, A. G. Soares, J. D. Stockand, “Snake venoms in drug discovery: Valuable therapeutic tools for life saving,” Toxins, vol. 11, no. 10. 2019.
• Y. Utkin, A. Siniavin, I. Kasheverov, V. Tsetlin, “Antiviral Effects of Animal Toxins: Is There a Way to Drugs?,” International Journal of Molecular Sciences, vol. 23, no. 7. 2022.
• L. Pinzi, Rastelli G., “Molecular docking: Shifting paradigms in drug discovery,” International Journal of Molecular Sciences, vol. 20, no. 18. 2019.
• V. Salmaso, Moro S., “Bridging molecular docking to molecular dynamics in exploring ligand-protein recognition process: An overview,” Frontiers in Pharmacology, vol. 9, no. 8, 2018.
• O. Troot, A. J. Olson, “Software News and Update AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading,” Journal of Computational Chemistry, vol. 31, no. 16, 2010.
• T. W. Wu, D. O. Tinker, “Phospholipase A2 from crotalus atrox venom. I. Purification and some properties,” Biochemistry, vol. 8, no. 4, 1969.
• K. Shimokawa, L. G. Jia, J. D. Shannon, J. W. Fox, “Isolation, sequence analysis, and biological activity of atrolysin E/D, the non-RGD disintegrin domain from Crotalus atrox venom,” Archives of biochemistry and biophysics, vol. 354, no. 2, 1998.
• R. M. Kini, C. Y. Koh, “Metalloproteases affecting blood coagulation, fibrinolysis and platelet aggregation from snake venoms: Definition and nomenclature of interaction sites,” Toxins, vol. 8, no. 10. 2016.
• E. Kikushima, Nakamura, S., Oshima, Y., Shibuya, T., Miao, J. Y., Hayashi, H., Araki, S., “Hemorrhagic activity of the vascular apoptosis-inducing proteins VAP1 and VAP2 from Crotalus atrox,” Toxicon, vol. 52, no. 4, 2008.