DOI: https://doi.org/10.14710/jksa.26.5.166-177

The potential of Myricitrin, a Flavonoid Compound in Eugenia polyantha from Indonesia, as an Antiviral Drug for SARS-Cov-2 through the Molecular Docking Analysis

1Department of Biochemistry, Faculty of Mathematics and Natural Sciences, IPB University, Kampus IPB Darmaga, Bogor, Jawa Barat, Indonesia

2Department of Biochemistry, Faculty of Mathematics and Natural Sciences, IPB University, Bogor, 16680, Indonesia

3Department of Applied Biosciences, Faculty of Agriculture, Ehime University, Ehime, Japan

Received: 18 Oct 2022; Revised: 9 Jun 2023; Accepted: 22 Jun 2023; Published: 31 Jul 2023.
Open Access Copyright 2023 Jurnal Kimia Sains dan Aplikasi under http://creativecommons.org/licenses/by-sa/4.0.

Citation Format:
Cover Image
Abstract

A Flavonoid glycoside compound, isolated and identified from E. polyantha as myricitrin, was analyzed as a ligand for its molecular binding activity against SARS-CoV-2 protein (receptor binding domain on Spike/RBD, main protease/nsp5, EndoRNAse, RNA-dependent-RNA-polymerase/RdRp), and its receptor, ACE2, and computationally assessed via molecular docking method. This study aims to determine the potential of myricitrin in E. polyantha from Indonesia as an antiviral drug for SARS-CoV-2 through molecular docking and molecular dynamic simulation analysis. The results showed that the myricitrin had the strongest binding affinity energy towards the three important SARS-CoV-2 proteins, namely endoRNAse, main protease (3CLpro), and RdRp with ∆G values of −9.60 kcal/mol, −8.40 kcal/mol, and −8.30 kcal/mol, respectively. These values are stronger than the comparator ligands of favipiravir (−5.60 kcal/mol), atazanavir (−7.20 kcal/mol), and remdesivir (−7.70 kcal/mol). This indicated that the compound has the potential as an inhibitor against 3CLpro, endoRNAse, and RdRp of SARS-CoV-2 proteins. This result was supported by the prediction made according to the Molprobity and PASS Online web servers, which showed that myricitrin has high bioactivity potential as an enzyme inhibitor (with a score of 0.38) and antiviral (with a score of 0.704).

Fulltext View|Download
Keywords: Eugenia polyantha; molecular docking; myricitrin; SARS-CoV-2
Funding: Deputy for Strengthening Research and Development, Ministry of Research and Technology of the Republic of Indonesia-Research and Innovation Agency (Kemenristek-BRIN)

Article Metrics:

Article Info
Section: Research Articles
Language : EN
Recent articles
The potential of Myricitrin, a Flavonoid Compound in Eugenia polyantha from Indonesia, as an Antiviral Drug for SARS-Cov-2 through the Molecular Docking Analysis Synthesis of Molecularly Imprinted Membrane Glucose for Selective Membrane Transport Biosensor based on Cellulose Acetate/Glutaraldehyde Membrane Electrodes for detection of organophosphorus pesticides More recent articles
Most cited articles
New Chemicals and Routes for the Preparation of Gelatin/HA Composites using the Wet Precipitation Method Analisis Pangan: Penentuan Angka Peroksida dan Asam Lemak Bebas pada Minyak Kedelai dengan Variasi Menggoreng Sintesis Silika Kristalin Menggunakan Surfaktan Cetiltrimetilamonium Bromida (CTAB) dan Trimetilamonium Klorida (TMACl) sebagai Pencetak Pori Dimerisasi Metilisoeugenol dengan Katalis HCl Pra-Standarisasi: Produksi dan Analisis Minyak Virgin Coconut Oil (VCO) More cited articles
  1. WHO Coronavirus (COVID-19) Dashboard, in, https://covid19.who.int/
  2. Vivi Setiawaty, Herman Kosasih, Yan Mardian, Emita Ajis, Endang Burni Prasetyowati, Siswanto, Muhammad Karyana, The identification of first COVID-19 cluster in Indonesia, The American Journal of Tropical Medicine and Hygiene, 103, 6, (2020), 2339-2342 https://doi.org/10.4269/ajtmh.20-0554
  3. Dewi Nur Aisyah, Chyntia Aryanti Mayadewi, Haniena Diva, Zisis Kozlakidis, Siswanto, Wiku Adisasmito, A spatial-temporal description of the SARS-CoV-2 infections in Indonesia during the first six months of outbreak, PloS ONE, 15, 12, (2020), e0243703 https://doi.org/10.1371/journal.pone.0243703
  4. Felipe Moura A. da Silva, Katia Pacheco A. da Silva, Luiz Paulo M. de Oliveira, Emmanoel V. Costa, Hector H. F. Koolen, Maria Lúcia B. Pinheiro, Antonia Queiroz L. de Souza, Afonso Duarte L. de Souza, Flavonoid glycosides and their putative human metabolites as potential inhibitors of the SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp), Memórias do Instituto Oswaldo Cruz, 115, (2020), e200207 https://doi.org/10.1590/0074-02760200207
  5. Raden Arthur Ario Lelono, Sanro Tachibana, Kazutaka Itoh, In vitro antioxidative activities and polyphenol content of Eugenia polyantha Wight grown in Indonesia, Pakistan Journal of Biological Sciences, 12, 24, (2009), 1564-1570 https://doi.org/10.3923/pjbs.2009.1564.1570
  6. Eisuke Kato, Ryo Nakagomi, Maria D. P. T. Gunawan-Puteri, Jun Kawabata, Identification of hydroxychavicol and its dimers, the lipase inhibitors contained in the Indonesian spice, Eugenia polyantha, Food Chemistry, 136, 3-4, (2013), 1239-1242 https://doi.org/10.1016/j.foodchem.2012.09.013
  7. R. A. A. Lelono, S. Tachibana, K. Itoh, Isolation of antifungal compounds from Gardenia jasminoides, Pakistan Journal of Biological Sciences, 12, 13, (2009), 949-956 https://doi.org/10.3923/pjbs.2009.949.956
  8. Elmar Krieger, Gert Vriend, New ways to boost molecular dynamics simulations, Journal of Computational Chemistry, 36, 13, (2015), 996-1007 https://doi.org/10.1002/jcc.23899
  9. Jrhau Lung, Yu‐Shih Lin, Yao‐Hsu Yang, Yu‐Lun Chou, Li‐Hsin Shu, Yu‐Ching Cheng, Hung Te Liu, Ching‐Yuan Wu, The potential chemical structure of anti‐SARS‐CoV‐2 RNA‐dependent RNA polymerase, Journal of Medical Virology, 92, 6, (2020), 693-697 https://doi.org/10.1002/jmv.25761
  10. Christopher A. Lipinski, Lead- and drug-like compounds: the rule-of-five revolution, Drug Discovery Today: Technologies, 1, 4, (2004), 337-341 https://doi.org/10.1016/j.ddtec.2004.11.007
  11. Irini Doytchinova, Mariyana Atanasova, Iva Valkova, Georgi Stavrakov, Irena Philipova, Zvetanka Zhivkova, Dimitrina Zheleva-Dimitrova, Spiro Konstantinov, Ivan Dimitrov, Novel hits for acetylcholinesterase inhibition derived by docking-based screening on ZINC database, Journal of Enzyme Inhibition and Medicinal Chemistry, 33, 1, (2018), 768-776 https://doi.org/10.1080/14756366.2018.1458031
  12. Ajay N. Jain, Anthony Nicholls, Recommendations for evaluation of computational methods, Journal of Computer-Aided Molecular Design, 22, (2008), 133-139 https://doi.org/10.1007/s10822-008-9196-5
  13. Yudibeth Sixto‐López, Marlet Martínez‐Archundia, Drug repositioning to target NSP15 protein on SARS‐CoV‐2 as possible COVID‐19 treatment, Journal of Computational Chemistry, 42, 13, (2021), 897-907 https://doi.org/10.1002/jcc.26512
  14. In-Wook Hwang, Shin-Kyo Chung, Isolation and identification of myricitrin, an antioxidant flavonoid, from daebong persimmon peel, Preventive Nutrition and Food Science, 23, 4, (2018), 341-346 https://doi.org/10.3746/pnf.2018.23.4.341
  15. Zhenming Jin, Xiaoyu Du, Yechun Xu, Yongqiang Deng, Meiqin Liu, Yao Zhao, Bing Zhang, Xiaofeng Li, Leike Zhang, Chao Peng, Yinkai Duan, Jing Yu, Lin Wang, Kailin Yang, Fengjiang Liu, Rendi Jiang, Xinglou Yang, Tian You, Xiaoce Liu, Xiuna Yang, Fang Bai, Hong Liu, Xiang Liu, Luke W. Guddat, Wenqing Xu, Gengfu Xiao, Chengfeng Qin, Zhengli Shi, Hualiang Jiang, Zihe Rao, Haitao Yang, Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors, Nature, 582, (2020), 289-293 https://doi.org/10.1038/s41586-020-2223-y
  16. Youngchang Kim, Robert Jedrzejczak, Natalia I. Maltseva, Mateusz Wilamowski, Michael Endres, Adam Godzik, Karolina Michalska, Andrzej Joachimiak, Crystal structure of Nsp15 endoribonuclease NendoU from SARS‐CoV‐2, Protein Science, 29, 7, (2020), 1596-1605 https://doi.org/10.1002/pro.3873
  17. Yushun Wan, Jian Shang, Rachel Graham, Ralph S. Baric, Fang Li, Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus, Journal of Virology, 94, 7, (2020), https://doi.org/10.1128/jvi.00127-20
  18. Nicola E. Clarke, Martin J. Fisher, Karen E. Porter, Daniel W. Lambert, Anthony J. Turner, Angiotensin converting enzyme (ACE) and ACE2 bind integrins and ACE2 regulates integrin signalling, PloS ONE, 7, 4, (2012), e34747 https://doi.org/10.1371/journal.pone.0034747
  19. Xiuyuan Ou, Yan Liu, Xiaobo Lei, Pei Li, Dan Mi, Lili Ren, Li Guo, Ruixuan Guo, Ting Chen, Jiaxin Hu, Zichun Xiang, Zhixia Mu, Xing Chen, Jieyong Chen, Keping Hu, Qi Jin, Jianwei Wang, Zhaohui Qian, Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV, Nature Communications, 11, (2020), 1620 https://doi.org/10.1038/s41467-020-15562-9
  20. Fang Li, Wenhui Li, Michael Farzan, Stephen C. Harrison, Structure of SARS coronavirus spike receptor-binding domain complexed with receptor, Science, 309, 5742, (2005), 1864-1868 https://doi.org/10.1126/science.1116480
  21. Iqrar Ahmad, Rahul Pawara, Sanjay Surana, Harun Patel, The repurposed ACE2 inhibitors: SARS-CoV-2 entry blockers of Covid-19, Topics in Current Chemistry, 379, (2021), 40 https://doi.org/10.1007/s41061-021-00353-7
  22. Ting Xiao, Mengqi Cui, Caijuan Zheng, Ming Wang, Ronghao Sun, Dandi Gao, Jiali Bao, Shanfa Ren, Bo Yang, Jianping Lin, Xiaoping Li, Dongmei Li, Cheng Yang, Honggang Zhou, Myricetin inhibits SARS-CoV-2 viral replication by targeting Mpro and ameliorates pulmonary inflammation, Frontiers in Pharmacology, 12, (2021), 669642 https://doi.org/10.3389/fphar.2021.669642
  23. Joshua Adedeji Bolarin, Mercy Adaramodu Oluwatoyosi, Joshua Iseoluwa Orege, Emmanuel Ayodeji Ayeni, Yusuf Ajibola Ibrahim, Sherif Babatunde Adeyemi, Bashir Bolaji Tiamiyu, Lanre Anthony Gbadegesin, Toluwanimi Oluwadara Akinyemi, Chuks Kenneth Odoh, Happiness Ijeoma Umeobi, Adenike Bernice-Eloise Adeoye, Therapeutic drugs for SARS-CoV-2 treatment: Current state and perspective, International Immunopharmacology, 90, (2021), 107228 https://doi.org/10.1016/j.intimp.2020.107228
  24. Natalia Fintelman-Rodrigues, Carolina Q. Sacramento, Carlyle Ribeiro Lima, Franklin Souza da Silva, Andre C. Ferreira, Mayara Mattos, Caroline S. de Freitas, Vinicius Cardoso Soares, Suelen da Silva Gomes Dias, Jairo R. Temerozo, Milene Miranda, R. Aline Matos, Fernando A. Bozza, Nicolas Carels, Carlos Roberto Alves, Marilda M. Siqueira, Patricia T. Bozza, Thiago Moreno L. Souza, Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production (preprint), bioRxiv, (2020), https://doi.org/10.1101/2020.04.04.020925
  25. Otávio Augusto Chaves, Carolina Q. Sacramento, André C. Ferreira, Mayara Mattos, Natalia Fintelman-Rodrigues, Jairo R. Temerozo, Leonardo Vazquez, Douglas Pereira Pinto, Gabriel P. E. da Silveira, Laís Bastos da Fonseca, Heliana Martins Pereira, Aluana Santana Carlos, Joana C. d'Avila, João P. B. Viola, Robson Q. Monteiro, Patricia T. Bozza, Hugo Caire Castro-Faria-Neto, Thiago Moreno L. Souza, Atazanavir is a competitive inhibitor of SARS-CoV-2 Mpro, impairing variants replication in vitro and in vivo, Pharmaceuticals, 15, 1, (2021), 21 https://doi.org/10.3390/ph15010021
  26. Xiaoyu Xue, Hongwei Yu, Haitao Yang, Fei Xue, Zhixin Wu, Wei Shen, Jun Li, Zhe Zhou, Yi Ding, Qi Zhao, Xuejun C. Zhang, Ming Liao, Mark Bartlam, Zihe Rao, Structures of two coronavirus main proteases: implications for substrate binding and antiviral drug design, Journal of virology, 82, 5, (2008), 2515-2527 https://doi.org/10.1128/jvi.02114-07
  27. Usman Bacha, Jennifer Barrila, Adrian Velazquez-Campoy, Stephanie A. Leavitt, Ernesto Freire, Identification of novel inhibitors of the SARS coronavirus main protease 3CLpro, Biochemistry, 43, 17, (2004), 4906-4912 https://doi.org/10.1021/bi0361766
  28. Yan Gao, Liming Yan, Yucen Huang, Fengjiang Liu, Yao Zhao, Lin Cao, Tao Wang, Qianqian Sun, Zhenhua Ming, Lianqi Zhang, Ji Ge, Litao Zheng, Ying Zhang, Haofeng Wang, Yan Zhu, Chen Zhu, Tianyu Hu, Tian Hua, Bing Zhang, Xiuna Yang, Jun Li, Haitao Yang, Zhijie Liu, Luke W. Guddat, Quan Wang, Zhiyong Lou, Zihe Rao, Structure of the RNA-dependent RNA polymerase from COVID-19 virus, Science, 368, 6492, (2020), 779-782 https://doi.org/10.1126/science.abb7498
  29. Abdo A. Elfiky, SARS-CoV-2 RNA dependent RNA polymerase (RdRp) targeting: An in silico perspective, Journal of Biomolecular Structure and Dynamics, 39, 9, (2021), 3204-3212 https://doi.org/10.1080/07391102.2020.1761882
  30. Xiaominting Song, Lu Tan, Miao Wang, Chaoxiang Ren, Chuanjie Guo, Bo Yang, Yali Ren, Zhixing Cao, Yuzhi Li, Jin Pei, Myricetin: A review of the most recent research, Biomedicine & Pharmacotherapy, 134, (2021), 111017 https://doi.org/10.1016/j.biopha.2020.111017
  31. Susan A. Olender, Katherine K. Perez, Alan S. Go, Bindu Balani, Eboni G. Price-Haywood, Nirav S. Shah, Su Wang, Theresa L. Walunas, Shobha Swaminathan, Jihad Slim, BumSik Chin, Stéphane De Wit, Shamim M. Ali, Alex Soriano Viladomiu, Philip Robinson, Robert L. Gottlieb, Tak Yin Owen Tsang, I-Heng Lee, Hao Hu, Richard H. Haubrich, Anand P. Chokkalingam, Lanjia Lin, Lijie Zhong, B. Nebiyou Bekele, Robertino Mera-Giler, Chloé Phulpin, Holly Edgar, Joel Gallant, Helena Diaz-Cuervo, Lindsey E. Smith, Anu O. Osinusi, Diana M. Brainard, Jose I. Bernardino, Remdesivir for severe coronavirus disease 2019 (COVID-19) versus a cohort receiving standard of care, Clinical Infectious Diseases, 73, 11, (2021), e4166-e4174 https://doi.org/10.1093/cid/ciaa1041
  32. Ashleigh Shannon, Nhung Thi-Tuyet Le, Barbara Selisko, Cecilia Eydoux, Karine Alvarez, Jean-Claude Guillemot, Etienne Decroly, Olve Peersen, Francois Ferron, Bruno Canard, Remdesivir and SARS-CoV-2: Structural requirements at both nsp12 RdRp and nsp14 Exonuclease active-sites, Antiviral Research, 178, (2020), 104793 https://doi.org/10.1016/j.antiviral.2020.104793
  33. Toshie Manabe, Dan Kambayashi, Hiroyasu Akatsu, Koichiro Kudo, Favipiravir for the treatment of patients with COVID-19: a systematic review and meta-analysis, BMC Infectious Diseases, 21, (2021), 489 https://doi.org/10.1186/s12879-021-06164-x
  34. Inge Hamming, Wim Timens, M. L. C. Bulthuis, A. T. Lely, G. J. van Navis, Harry van Goor, Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis, The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland, 203, 2, (2004), 631-637 https://doi.org/10.1002/path.1570
  35. Muchtaridi Muchtaridi, M. Fauzi, Nur Kusaira Khairul Ikram, Amirah Mohd Gazzali, Habibah A. Wahab, Natural flavonoids as potential angiotensin-converting enzyme 2 inhibitors for anti-SARS-CoV-2, Molecules, 25, 17, (2020), 3980 https://doi.org/10.3390/molecules25173980
  36. P. S. Kulkarni, Y. S. Walunj, N. D. Dongare, Theoretical Validation of Medicinal Properties of Ocimum sanctum, The Chemist, 92, 1, (2021), 1-7
  37. S. Parasuraman, Prediction of activity spectra for substances, Journal of Pharmacology & Pharmacotherapeutics, 2, 1, (2011), 52-53 https://doi.org/10.4103/0976-500X.77119

Last update:

No citation recorded.

Last update: 2024-11-20 12:41:03

No citation recorded.