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Investigation of Active Compounds in Propolis Structure Against Sars Cov-2 Main Protease by Molecular Docking Method: In Silico Study

Year 2024, Volume: 27 Issue: 1, 46 - 55, 28.02.2024

Erkan Öner İlter Demirhan Serap Yalın Ergul Belge Kurutas

https://doi.org/10.18016/ksutarimdoga.vi.1093707

Abstract

It was aimed to investigate the active ingredients limonin, quercetin and kaempferol in propolis against SARS-CoV-2 main protease(MPro) using in silico methods. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) screening of ligands assists US to state their absorption properties, toxicity, and drug-likeness. Ligand molecules obtained from PubChem in smiles format were loaded on SWISSADME and PROTOX-II webservers for ADMET screening. The three compounds in propolis were obtained from the PubChem database. Compounds were located at the active site of the SARS-CoV-2 MPro receptor with PDB ID:6LU7. Molecular docking work was done with Autodock program. Molecular docking results were found as -8.7 kcal/mol in limonin, -7.5 kcal/mol in quercetin and -7.7 kcal/mol in kaempferol. In silico ADMET estimation showed they have a potential for antiviral therapy. In conclusion, we thought that propolis active components limonin, quercetin and kaempferol have the potential to be a SARS CoV-2 MPro inhibitor.

Keywords

Sars Cov 2 Main Protease Propolis COVID-19 ADMET

References

  • Arokiyaraj, S., Stalin, A., Kannan, B.S., Shin, H. (2020). Geranii Herba as a Potential Inhibitor of SARS-CoV-2 Main 3CL pro, Spike RBD, and Regulation of Unfolded Protein Response: An In Silico Approach. Antibiotics (Basel). 9(12), 863-872. https://doi.org/10.3390/antibiotics9120863.
  • Banerjee, P., Eckert, O.A., Schrey, A.K., Preissner, R. (2018). ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Research, 46(2), 257–263. https://doi.org/10.1093/nar/gky318
  • Bell, E.W. & Zhang, Y. (2019). DockRMSD: an opensource tool for atom mapping and RMSD calculation of symmetric molecules through graph isomorphism. Journal of Cheminformatics, 11(1), 40. doi:10.1186/s13321-019-0362-7
  • Diana, M., Raij, T., Melis, M. (2017). Rehabilitating the addicted brain with transcranial magnetic stimulation. Nature Reviews Neuroscience. 18, 685–693. https://doi.org/10.1038/nrn.2017.113.
  • Gulcin, I., Bursal, E., Sehitoglu, H.M., Bilsel, M., Goren, A.C. (2010). Polyphenol contents and antioxidant activity of lyophilized aqueous extract of propolis from Erzurum, Turkey. Food and Chemical Toxicology, 48 (8-9), 2227-2238. doi: 10.1016/j.fct.2010.05.053.
  • Hegazi, A.G., Abd, El, Hady, F.K., Abd, Allah, F.A. (2000). Chemical composition and antimicrobial activity of European propolis. Zeitschrift für Naturforschung. 56, 82-88. https://doi.org/10.1515/ znc-2000-1-214.
  • Hofmann, H., Pohlmann, S. (2004). Cellular entry of the SARS coronavirus. Trends Microbiolology,12(4), 466-472. https://doi.org/ 10.1016/ j.tim.2004.08.008.
  • Jin, Z., Du, X., Xu, Y., Deng, Y., Liu, M., Zhao, Y., Zhang, B., et al. (2020). Structure of M pro from SARS-CoV-2 and discovery of its inhibitors. Nature, 582, 289–293.
  • Khan, N.S., Kumam, P., & Thounthong, P. (2021). Magnetic field promoted an irreversible process of water-based nanocomposites with heat and mass transfer flow. Scientific Reports, 11(1),1692. https://doi.org/10.1038/s41598-020-80554-0.
  • Laskowski, R.A. (1995). A program for visualizing molecular surfaces, cavities, and intermolecular interactions. Journal of Molecular Graphics, 13, 323–330. https://doi.org/ 10.1016/0263-7855(95) 00073-9.
  • Luo, E., Zhang, D., Luo, H., Liu, B., Zhao, K., Zhao, Y., Wang, Y. (2020). Treatment efficacy analysis of traditional Chinese medicine for novel coronavirus pneumonia (COVID‐19): An empirical study from Wuhan, Hubei Province, China. Chinese Medicine, 15, 34-47. https://doi.org/10.1186/s13020-020-00317-x.
  • Malik, W., Sircar, Y.S., Bhat, S., Sharun, S., Dhama, K., Dadar, M., Tiwari, R., Chaicumpa, W. (2020). Emerging novel Coronavirus (2019-nCoV) - current scenario, evolutionary perspective based on genome analysis and recent developments. Veterinary Quarterly, 40, 1-12. https://doi.org/10.1080/ 01652176.2020.1727993.
  • Marcucci, M.C. (1995). Propolis: Chemical Composition, Biological Properties, And Therapeutic Activity. In Apidologie, 26, 83-99. https://doi.org/10.1051/apido:19950202.
  • 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. doi:10.1002/jcc.21256
  • Onodera, K., Satou, K., Hirota, H. (2007). Evaluations of molecular docking programs for virtual screening. Journal of Chemical Information and Modeling, 47, 1609–1618. https://doi.org/ 10.1021/ ci7000378.
  • Pajouhesh, H. & Lenz, G.R. (2005). Medicinal chemical properties of successful central nervous system drugs. NeuroRx. 2(4), 541-553. https://doi.org/ 10.1602/neurorx.2.4.541.
  • Rodríguez-Morales, A.J., MacGregor, K., Kanagarajah, S., Patel, D., Schlagenhauf, P. (2020). Going global – travel and the 2019 novel coronavirus. Travel Medicine and Infectious Disease, 33, 10:15-78. https://doi.org/ 10.1016/j.tmaid.2020.101578.
  • Sibel, S. & Semiramis, K. (2005). The chemical composition and antibacterial activity of propolis were collected by three different races of honeybees in the same region. In Journal of Ethnopharmacology, 99 (1), 69–73. https://doi.org/ 10.1016/j.jep.2005.01.046.
  • Trott, O. & 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,31,455–461. https://doi.org/ 10.1002/ jcc.21334.
  • Vardeny, O., Madjid, M., Solomon, S.D. (2020). Applying Flu Lessons to COVID-19 During a Time of Uncertainty. Circulation, 141 (21),1667-1669. https://doi.org/ 10.1161/.120.046837.
  • Vardhan, S. & Sahoo, S.K. (2020). In silico ADMET and molecular docking study on searching potential inhibitors from limonoids and triterpenoids for COVID-19. Computers in Biology and Medicine,124: 103936. https://doi.org/ 10.1016/ j.compbiomed.2020.103936.
  • Yang, L., Li, Y.T., Miao, J., Wang, L., Fu, H., Li, Q., Wen, W.B., Zhang, Z.Y., Song, R.W., Liu, X.G., Wang, H.W., Cui, H.T. (2020). Network pharmacology studies on the effect of Chai-Ling decoction in coronavirus disease. Traditional Medicine Research, 5 (3), 145. https://doi.org/ 20200501.
  • Yang, L., Wen, K.S., Ruan, X., Zhao, Y.X., Wei, F., Wang, Q. (2018). Response of plant secondary metabolites to environmental factors. Molecules, 23, 1-26. https://doi.org/10.3390/molecules23040762

Sars Cov-2 Ana Proteaz'da Propolis Yapısındaki Aktif Bileşiklerin Moleküler Yerleştirme Yöntemiyle Araştırılması: In Silico Çalışması

Year 2024, Volume: 27 Issue: 1, 46 - 55, 28.02.2024

Erkan Öner İlter Demirhan Serap Yalın Ergul Belge Kurutas

https://doi.org/10.18016/ksutarimdoga.vi.1093707

Abstract

Propolisin aktif bileşikleri olan limonin, quercetin ve kaempferol'ü SARS-CoV-2 ana proteaza (MPro) karşı in silico yöntemlerle araştırması amaçlandı. Ligandların absorpsiyon, dağılım, metabolizma, atılım ve toksisite (ADMET) taraması, absorpsiyon özelliklerini, toksisitesini ve ilaca benzerliğini belirtmesine yardımcı olur. PubChem'den smiless formatında elde edilen ligand molekülleri, ADMET taraması için SWISSADME ve PROTOX-II web sunucularına yüklendi. Propolisteki üç bileşik, PubChem veritabanından elde edildi. Bileşikler, PDB ID:6LU7 ile SARS-CoV-2 MPro reseptörünün aktif bölgesine yerleştirildi. Autodock programı ile moleküler yerleştirme çalışması yapıldı. Moleküler yerleştirme sonuçları limoninde -8,7 kcal/mol, quercetin'de -7,5 kcal/mol ve kaempferol'de -7,7 kcal/mol olarak bulundu. In silico ADMET tahmini, antiviral tedavi potansiyeline sahip olduklarını gösterdi. Sonuç olarak, propolis aktif bileşenleri limonin, quercetin ve kaempferol'ün SARS CoV-2 MPro inhibitörü olma potansiyeline sahip olabileceği düşünülmektedir.

Keywords

Sars-Cov-2 Ana Proteaz Propolis COVİD-19 ADMET

References

  • Arokiyaraj, S., Stalin, A., Kannan, B.S., Shin, H. (2020). Geranii Herba as a Potential Inhibitor of SARS-CoV-2 Main 3CL pro, Spike RBD, and Regulation of Unfolded Protein Response: An In Silico Approach. Antibiotics (Basel). 9(12), 863-872. https://doi.org/10.3390/antibiotics9120863.
  • Banerjee, P., Eckert, O.A., Schrey, A.K., Preissner, R. (2018). ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Research, 46(2), 257–263. https://doi.org/10.1093/nar/gky318
  • Bell, E.W. & Zhang, Y. (2019). DockRMSD: an opensource tool for atom mapping and RMSD calculation of symmetric molecules through graph isomorphism. Journal of Cheminformatics, 11(1), 40. doi:10.1186/s13321-019-0362-7
  • Diana, M., Raij, T., Melis, M. (2017). Rehabilitating the addicted brain with transcranial magnetic stimulation. Nature Reviews Neuroscience. 18, 685–693. https://doi.org/10.1038/nrn.2017.113.
  • Gulcin, I., Bursal, E., Sehitoglu, H.M., Bilsel, M., Goren, A.C. (2010). Polyphenol contents and antioxidant activity of lyophilized aqueous extract of propolis from Erzurum, Turkey. Food and Chemical Toxicology, 48 (8-9), 2227-2238. doi: 10.1016/j.fct.2010.05.053.
  • Hegazi, A.G., Abd, El, Hady, F.K., Abd, Allah, F.A. (2000). Chemical composition and antimicrobial activity of European propolis. Zeitschrift für Naturforschung. 56, 82-88. https://doi.org/10.1515/ znc-2000-1-214.
  • Hofmann, H., Pohlmann, S. (2004). Cellular entry of the SARS coronavirus. Trends Microbiolology,12(4), 466-472. https://doi.org/ 10.1016/ j.tim.2004.08.008.
  • Jin, Z., Du, X., Xu, Y., Deng, Y., Liu, M., Zhao, Y., Zhang, B., et al. (2020). Structure of M pro from SARS-CoV-2 and discovery of its inhibitors. Nature, 582, 289–293.
  • Khan, N.S., Kumam, P., & Thounthong, P. (2021). Magnetic field promoted an irreversible process of water-based nanocomposites with heat and mass transfer flow. Scientific Reports, 11(1),1692. https://doi.org/10.1038/s41598-020-80554-0.
  • Laskowski, R.A. (1995). A program for visualizing molecular surfaces, cavities, and intermolecular interactions. Journal of Molecular Graphics, 13, 323–330. https://doi.org/ 10.1016/0263-7855(95) 00073-9.
  • Luo, E., Zhang, D., Luo, H., Liu, B., Zhao, K., Zhao, Y., Wang, Y. (2020). Treatment efficacy analysis of traditional Chinese medicine for novel coronavirus pneumonia (COVID‐19): An empirical study from Wuhan, Hubei Province, China. Chinese Medicine, 15, 34-47. https://doi.org/10.1186/s13020-020-00317-x.
  • Malik, W., Sircar, Y.S., Bhat, S., Sharun, S., Dhama, K., Dadar, M., Tiwari, R., Chaicumpa, W. (2020). Emerging novel Coronavirus (2019-nCoV) - current scenario, evolutionary perspective based on genome analysis and recent developments. Veterinary Quarterly, 40, 1-12. https://doi.org/10.1080/ 01652176.2020.1727993.
  • Marcucci, M.C. (1995). Propolis: Chemical Composition, Biological Properties, And Therapeutic Activity. In Apidologie, 26, 83-99. https://doi.org/10.1051/apido:19950202.
  • 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. doi:10.1002/jcc.21256
  • Onodera, K., Satou, K., Hirota, H. (2007). Evaluations of molecular docking programs for virtual screening. Journal of Chemical Information and Modeling, 47, 1609–1618. https://doi.org/ 10.1021/ ci7000378.
  • Pajouhesh, H. & Lenz, G.R. (2005). Medicinal chemical properties of successful central nervous system drugs. NeuroRx. 2(4), 541-553. https://doi.org/ 10.1602/neurorx.2.4.541.
  • Rodríguez-Morales, A.J., MacGregor, K., Kanagarajah, S., Patel, D., Schlagenhauf, P. (2020). Going global – travel and the 2019 novel coronavirus. Travel Medicine and Infectious Disease, 33, 10:15-78. https://doi.org/ 10.1016/j.tmaid.2020.101578.
  • Sibel, S. & Semiramis, K. (2005). The chemical composition and antibacterial activity of propolis were collected by three different races of honeybees in the same region. In Journal of Ethnopharmacology, 99 (1), 69–73. https://doi.org/ 10.1016/j.jep.2005.01.046.
  • Trott, O. & 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,31,455–461. https://doi.org/ 10.1002/ jcc.21334.
  • Vardeny, O., Madjid, M., Solomon, S.D. (2020). Applying Flu Lessons to COVID-19 During a Time of Uncertainty. Circulation, 141 (21),1667-1669. https://doi.org/ 10.1161/.120.046837.
  • Vardhan, S. & Sahoo, S.K. (2020). In silico ADMET and molecular docking study on searching potential inhibitors from limonoids and triterpenoids for COVID-19. Computers in Biology and Medicine,124: 103936. https://doi.org/ 10.1016/ j.compbiomed.2020.103936.
  • Yang, L., Li, Y.T., Miao, J., Wang, L., Fu, H., Li, Q., Wen, W.B., Zhang, Z.Y., Song, R.W., Liu, X.G., Wang, H.W., Cui, H.T. (2020). Network pharmacology studies on the effect of Chai-Ling decoction in coronavirus disease. Traditional Medicine Research, 5 (3), 145. https://doi.org/ 20200501.
  • Yang, L., Wen, K.S., Ruan, X., Zhao, Y.X., Wei, F., Wang, Q. (2018). Response of plant secondary metabolites to environmental factors. Molecules, 23, 1-26. https://doi.org/10.3390/molecules23040762
There are 23 citations in total.

Details

Primary Language English
Subjects Structural Biology
Journal Section RESEARCH ARTICLE
Authors

Erkan Öner 0000-0002-6332-6484

İlter Demirhan 0000-0003-0054-7893

Serap Yalın 0000-0002-1286-2172

Ergul Belge Kurutas 0000-0002-6653-4801

Early Pub Date October 13, 2023
Publication Date February 28, 2024
Submission Date March 26, 2022
Acceptance Date August 22, 2022
Published in Issue Year 2024Volume: 27 Issue: 1

Cite

APA Öner, E., Demirhan, İ., Yalın, S., Belge Kurutas, E. (2024). Investigation of Active Compounds in Propolis Structure Against Sars Cov-2 Main Protease by Molecular Docking Method: In Silico Study. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 27(1), 46-55. https://doi.org/10.18016/ksutarimdoga.vi.1093707
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