DOI: https://doi.org/10.14710/jksa.25.10.382-393

Screening of Secondary Metabolite Compounds of Gorontalo Traditional Medicinal Plants Using the In Silico Method as a Candidate for SARS-CoV-2 Antiviral

Department of Chemistry, Faculty of Sciences and Mathematics, Universitas Negeri Gorontalo, Gorontalo, Indonesia

Received: 6 Oct 2022; Revised: 13 Dec 2022; Accepted: 24 Dec 2022; Available online: 25 Dec 2022; Published: 12 Jan 2023.
Open Access Copyright 2022 Jurnal Kimia Sains dan Aplikasi under http://creativecommons.org/licenses/by-sa/4.0.

Citation Format:
Cover Image
Abstract

COVID-19 is a disease that caused a prolonged pandemic in many countries caused by the SARS-CoV-2 virus. This study aims to identify the antiviral potential of secondary metabolites in Gorontalo traditional medicinal plants, which are believed to have the ability to inhibit the main protease protein of this virus. The methods used in this research were molecular docking and molecular dynamic. The main protease proteins for SARS-CoV-2 used based on the homology modeling results were 3V3M and 7TE0. The results of the active compounds in the paxlovid drug were also compared to obtain accurate data comparisons. The validation of the docking method on the 3V3M protein using the natural ligand 0EN revealed an RMSD of 0.75 Å. The RMSD value for validating the 7TE0 protein and natural ligand 4WI was 1.65 Å. The best molecular docking results were obtained using physalin F with a binding affinity of −10.3 kcal/mol for the 3V3M protein and physalin J with a binding affinity of −8.9 kcal/mol for the 7TE0 protein. The outcomes of the molecular dynamic method on the best complexes were determined by examining the value of changes in system energy, changes in system temperature, changes in system pressure, RMSD, RMSF, and bond-free energy (ΔG) of the complex. The standard 0EN ligand had a ΔG of −26.53 kcal/mol, while the standard 4WI ligand had a ΔG of −47.16 kcal/mol. The ΔG of the 3V3M-physalin F and 3V3M-physalin J complexes were respectively −28.22 kcal/mol and −26.62 kcal/mol. The ΔG of the 7TE0-Vitexin 2”-O-gallate and 7TE0-physalin J complexes were found to be −28.08 kcal/mol and −26.62 kcal/mol, respectively. The ΔG produced in paxlovid with complexes 3V3M and 7TE0 was −19.38 kcal/mol and −25.44 kcal/mol, respectively. Physalin F, physalin J, and Vitexin 2”-O-gallate have great potential to become SARS-CoV-2 inhibitor agents. However, in terms of structural stability and binding-active residues, these three compounds do not outperform the active substance in paxlovid.

Note: This article has supplementary file(s).

Fulltext View|Download |  Research Results
Supplementary Table
Subject
Type Research Results
  Download (207KB)    Indexing metadata
Keywords: Antivirals; SARS-CoV-2; molecular docking; molecular dynamics; COVID-19
Funding: Universitas Negeri Gorontalo

Article Metrics:

Article Info
Section: Research Articles
Language : EN
Recent articles
Green Synthesis of Copper Nanoparticles Using Red Dragon Fruit (Hylocereus polyrhizus) Extract and Its Antibacterial Activity for Liquid Disinfectant Effect of the Amount of Carbon in the Fe3O4@ZnO-C Nanocomposites on Its Structure and Magnetic Properties Screening of Secondary Metabolite Compounds of Gorontalo Traditional Medicinal Plants Using the In Silico Method as a Candidate for SARS-CoV-2 Antiviral More recent articles
Most cited articles
Innovation of Carbon from Pectin Templated in Fabrication of Interlayer-free Silica-Pectin Membrane Sintesis 3-(3,4-Dimetoksi Fenil)-1-Propanol Melalui Hidroborasi Metileugenol Menggunakan H3B:Dietileter Synthesis of 4-Hydroxy-2-Methylchalcone from meta-Cresol Formilation Product and Its Activities as an Antibacteria Skrining Metabolit Sekunder Bakteri Endofit yang Berfungsi sebagai Antidiabetes dari Daun Mimba (Azadirachta Indica) Molecular Docking of Interaction between E-Cadherin Protein and Conformational Structure of Cyclic Peptide ADTC3 (Ac-CADTPC-NH2) Simulated on 20 ns More cited articles
  1. Muhammad Adnan Shereen, Suliman Khan, Abeer Kazmi, Nadia Bashir, Rabeea Siddique, COVID-19 infection: Emergence, transmission, and characteristics of human coronaviruses, Journal of Advanced Research, 24, (2020), 91-98 https://doi.org/10.1016/j.jare.2020.03.005
  2. Zheng Gong, Jun-Wei Zhu, Cui-Ping Li, Shuai Jiang, Li-Na Ma, Bi-Xia Tang, Dong Zou, Mei-Li Chen, Yu-Bin Sun, Shu-Hui Song, Zhang Zhang, Jing-Fa Xiao, Xue. Yong-Biao, Bao. Yi-Ming, Zheng-Lin Du, Wen-Ming Zhao, An online coronavirus analysis platform from the National Genomics Data Center, Zoological Research, 41, 6, (2020), 705 https://doi.org/10.24272/j.issn.2095-8137.2020.065
  3. Md. Rayhan Chowdhury, Md. Atik Mas-Ud, Md. Roushan Ali, Mst. Fatamatuzzohora, Ajmeri Sultana Shimu, Md. Anamul Haq, Md. Ashikul Islam, Md. Firose Hossain, Md. Hosenuzzaman, Md. Mominul Islam, Harmful effects of COVID-19 on major human body organs: a review, Journal of Pure and Applied Microbiology, 15, 2, (2021), 500-511 https://doi.org/10.22207/JPAM.15.2.14
  4. Devendra Saran, Parminder Kaur, Arshida Khatun, How does COVID-19 invade the human body, The Science World, 1, 2, (2021), 4-9
  5. Ifat Hanifah, Dody Riswanto, Siti Nurbani, The Impact of The Covid-19 Pandemic on The Economic, Social, Cultural, And Employment of Indonesian Civil Society, Journal of Advanced Research in Dynamical and Control Systems, 12, 2, (2020), 3112-3117 https://doi.org/10.5373/JARDCS/V12I2/S20201430
  6. Imrana Qadeer, K. B. Saxena, P. M. Arathi, Universalising Healthcare in India: From Care to Coverage, 1 ed., Springer Singapore, 2021, https://doi.org/10.1007/978-981-16-5872-3
  7. Linlin Zhang, Daizong Lin, Xinyuanyuan Sun, Ute Curth, Christian Drosten, Lucie Sauerhering, Stephan Becker, Katharina Rox, Rolf Hilgenfeld, Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors, Science, 368, 6489, (2020), 409-412 https://doi.org/10.1126/science.abb3405
  8. Wen Cui, Kailin Yang, Haitao Yang, Recent progress in the drug development targeting SARS-CoV-2 main protease as treatment for COVID-19, Frontiers in Molecular Biosciences, 7, (2020), 616341 https://doi.org/10.3389/fmolb.2020.616341
  9. Shamaila Kausar, Fahad Said Khan, Muhammad Ishaq Mujeeb Ur Rehman, Muhammad Akram, Muhammad Riaz, Ghulam Rasool, Abdul Hamid Khan, Iqra Saleem, Saba Shamim, Arif Malik, A review: Mechanism of action of antiviral drugs, International Journal of Immunopathology and Pharmacology, 35, (2021), 1-12 https://doi.org/10.1177/20587384211002621
  10. Jennifer Couzin-Frankel, in: Science, American Association for the Advancement of Science, 2021, https://doi.org/10.1126/science.acx9605
  11. Io Antonopoulou, Eleftheria Sapountzaki, Ulrika Rova, Paul Christakopoulos, Inhibition of the main protease of SARS-CoV-2 (Mpro) by repurposing/designing drug-like substances and utilizing nature’s toolbox of bioactive compounds, Computational and Structural Biotechnology Journal, 20, (2022), 1306-1344 https://doi.org/10.1016/j.csbj.2022.03.009
  12. Bethany Halford, in: Chemical & Engineering News, American Chemical Society, 2022
  13. Wen Wen, Chen Chen, Jiake Tang, Chunyi Wang, Mengyun Zhou, Yongran Cheng, Xiang Zhou, Qi Wu, Xingwei Zhang, Zhanhui Feng, Mingwei Wang, Qin Mao, Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and Paxlovid) for COVID-1: a meta-analysis, Annals of Medicine, 54, 1, (2022), 516-523 https://doi.org/10.1080/07853890.2022.2034936
  14. Firtyane Lihawa, Ramli Utina, Wirnangsi Uno, Malonda Maksud, Riset khusus eksplorasi pengetahuan lokal etnomedisin dan tumbuhan obat di indonesia berbasis komunitas, Universitas Negeri Gorontalo, Gorontalo, 2012
  15. Yulia Vera, Susi Yanti, Penyuluhan Pemanfaatan Tanaman Obat dan Obat Tradisional Indonesia Untuk Pencegahan dan Penanggulangan Penyakit Hipertensi di Desa Salam Bue, Jurnal Education and Development, 8, 1, (2020), 11-14
  16. Novri Y. Kandowangko, Kajian Etnobotani Tanaman Obat oleh Masyarakat Kabupaten Bonebolango Provinsi Gorontalo, Gorontalo State University, Gorontalo, 2014
  17. Garrett M. Morris, Ruth Huey, William Lindstrom, Michel F. Sanner, Richard K. Belew, David S. Goodsell, Arthur J. Olson, AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility, Journal of Computational Chemistry, 30, 16, (2009), 2785-2791 https://doi.org/10.1002/jcc.21256
  18. Oleg Trott, Arthur J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, Journal of Computational Chemistry, 31, 2, (2010), 455-461 https://doi.org/10.1002/jcc.21334
  19. Dassault Systemes Biovia, BIOVIA discovery studio, in: Dassault Systèmes, 2020
  20. A. Orin, R. Johnston, J. Clear, B. Skwarecki, Behind The App: The Story of Notepad++, Lifehacker Australia, 18, (2015)
  21. Demian Riccardi, Jerry M. Parks, Alexander Johs, Jeremy C. Smith, HackaMol: An Object-Oriented Modern Perl Library for Molecular Hacking on Multiple Scales, Journal of Chemical Information and Modeling, 55, 4, (2015), 721-726 https://doi.org/10.1021/ci500359e
  22. Noel M. O'Boyle, Michael Banck, Craig A. James, Chris Morley, Tim Vandermeersch, Geoffrey R. Hutchison, Open Babel: An open chemical toolbox, Journal of Cheminformatics, 3, 1, (2011), 1-14 https://doi.org/10.1186/1758-2946-3-33
  23. L. L. C. Schrödinger, The PyMOL molecular graphics system, version 1.8, in: Schrödinger, L. L. C., 2015
  24. Mark James Abraham, Teemu Murtola, Roland Schulz, Szilárd Páll, Jeremy C. Smith, Berk Hess, Erik Lindahl, GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers, SoftwareX, 1, (2015), 19-25 https://doi.org/10.1016/j.softx.2015.06.001
  25. P. J. Turner, XMGRACE, Version 5.1. 19, in: Center for Coastal and Land-Margin Research, Oregon Graduate Institute of Science and Technology, Beaverton, OR, 2005
  26. Shuhui Song, Lina Ma, Dong Zou, Dongmei Tian, Cuiping Li, Junwei Zhu, Meili Chen, Anke Wang, Yingke Ma, Mengwei Li, Xufei Teng, Ying Cui, Guangya Duan, Mochen Zhang, Tong Jin, Chengmin Shi, Zhenglin Du, Yadong Zhang, Chuandong Liu, Rujiao Li, Jingyao Zeng, Lili Hao, Shuai Jiang, Hua Chen, Dali Han, Jingfa Xiao, Zhang Zhang, Wenming Zhao, Yongbiao Xue, Yiming Bao, The global landscape of SARS-CoV-2 genomes, variants, and haplotypes in 2019nCoVR, Genomics, Proteomics & Bioinformatics, 18, 6, (2020), 749-759 https://doi.org/10.1016/j.gpb.2020.09.001
  27. Siqi Wu, Chang Tian, Panpan Liu, Dongjie Guo, Wei Zheng, Xiaoqiang Huang, Yang Zhang, Lijun Liu, Effects of SARS‐CoV‐2 mutations on protein structures and intraviral protein–protein interactions, Journal of Medical Virology, 93, 4, (2020), 2132-2140 https://doi.org/10.1002/jmv.26597
  28. María J. R. Yunta, How important is to account for water when modeling biomolecular complexes, American Journal of Modeling and Optimization, 3, 3, (2015), 68-86
  29. G. Madhavi Sastry, Matvey Adzhigirey, Tyler Day, Ramakrishna Annabhimoju, Woody Sherman, Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments, Journal of Computer-Aided Molecular Design, 27, 3, (2013), 221-234 https://doi.org/10.1007/s10822-013-9644-8
  30. Neni Frimayanti, Musyirna Rahmah Nasution, Elsa Etavianti, Molecular docking and molecular dynamic simulation of 1, 5-benzothiazepine chalcone derivative compounds as potential inhibitors for Zika virus helicase, Jurnal Riset Kimia, 12, 1, (2021), 44-52 https://doi.org/10.25077/jrk.v12i1.365
  31. Kresten Lindorff‐Larsen, Stefano Piana, Kim Palmo, Paul Maragakis, John L. Klepeis, Ron O. Dror, David E. Shaw, Improved side‐chain torsion potentials for the Amber ff99SB protein force field, Proteins: Structure, Function, and Bioinformatics, 78, 8, (2010), 1950-1958 https://doi.org/10.1002/prot.22711
  32. Fauzan Zein Muttaqin, Halim Ismail, Hubbi Nasrullah Muhammad, Studi molecular docking, molecular dynamic, dan prediksi toksisitas senyawa turunan alkaloid naftiridin sebagai inhibitor protein kasein kinase 2-Α pada kanker leukemia, Pharmacoscript, 2, 1, (2019), 49-64
  33. P. G. Bolhuis, Sampling kinetic protein folding pathways using all-atom models, in: Computer Simulations in Condensed Matter Systems: From Materials to Chemical Biology Volume 1, Springer, 2006, https://doi.org/10.1007/3-540-35273-2_11
  34. Priyashi Rao, Arpit Shukla, Paritosh Parmar, Rakesh M. Rawal, Baldev Patel, Meenu Saraf, Dweipayan Goswami, Reckoning a fungal metabolite, Pyranonigrin A as a potential Main protease (Mpro) inhibitor of novel SARS-CoV-2 virus identified using docking and molecular dynamics simulation, Biophysical Chemistry, 264, 106425, (2020), 1-11 https://doi.org/10.1016/j.bpc.2020.106425
  35. Frithjof Godschalk, Samuel Genheden, Pär Söderhjelm, Ulf Ryde, Comparison of MM/GBSA calculations based on explicit and implicit solvent simulations, Physical Chemistry Chemical Physics, 15, 20, (2013), 7731-7739 https://doi.org/10.1039/C3CP00116D

Last update:

No citation recorded.

Last update: 2024-04-26 18:32:05

No citation recorded.