Kajian Farmakoinformatika Senyawa Brazilin dan 3-O-Methyl Brazilin Caesalpinia sappan Sebagai Terapi Demam Berdarah Dengue


Dewi Ratih Tirto Sari(1*), Heny Yusuf(2), Laily Sifaiyah(3), Nur Dina Camelia(4), Yohanes Bare(5)

(1) Program Studi Farmasi Fakultas Ilmu Kesehatan Universitas Ibrahimy, Situbondo, Jawa Timur, Indonesia
(2) Program Studi Farmasi Fakultas Ilmu Kesehatan Universitas Ibrahimy, Situbondo, Jawa Timur, Indonesia
(3) Program Studi Farmasi Fakultas Ilmu Kesehatan Universitas Ibrahimy, Situbondo, Jawa Timur, Indonesia
(4) Program Studi Kebidanan Fakultas Ilmu Kesehatan Universitas Ibrahimy, Situbondo, Jawa Timur, Indonesia
(5) Program Studi Pendidikan Biologi Fakultas Keguruan dan Ilmu Pendidikan Universitas Nusa Nipa, Nusa Tenggara Timur, Indonesia
(*) Corresponding Author

Abstract


Demam berdarah Dengue (DBD) merupakan penyakit tropis yang diakibatkan oleh gigitan nyamuk yang terinfeksi oleh virus DENV. Beberapa tanaman herbal dapat digunakan untuk mengatasi demam berdarah baik upaya preventif maupun kuratif. Kayu secang merupakan salah satu tanaman herbal kayu yang memiliki berbagai aktivitas biologis, utamanya sebagai immunomodulator dan antivirus. Penelitian ini bertujuan untuk mengidentifikasi aktivitas brazilin dan 3-O-methyl brazilin sebagai obat terapi demam berdarah melalui kajian komputasi. Pendekatan molecular docking digunakan dalam studi penelitian ini. Senyawa brazilin dan 3-O-methyl brazilin diunduh dari database PubChem dan diinteraksikan dengan protein non- structural-5 (NS-5) yang didapatkan dari database PDB. Pemodelan docking dilakukan dengan Molegro virtual Docker versi 5.0 dan dianalisis dengan PyMol 2.2 dan Discovery studio versi 21.1.1. Hasil interaksi menunjukkan bahwa brazilin dan 3-O-methyl brazilin berikatan dengan protein NS-5 di sisi aktif guanosine triphosphate dan daerah RNA dependent RNA polymerase (RdRP). Pengikatan kedua senyawa aktif ini menyebabkan tidak terjadinya replikasi virus DENV pada sel inang dan berpotensi sebagai penghambat infeksi DENV. Berdasarkan analisis in silico, disimpulkan bahwa brazilin dan 3-O-methyl brazilin berpotensi sebagai agen terapi demam berdarah, studi in vitro perlu dilakukan untuk pembuktian lebih lanjut. 


Keywords


brazilin, demam berdarah dengue, DENV, kayu secang, protein NS-5

Full Text:

PDF

References


S. Hasan, S. F. Jamdar, M. Alalowi, and S. M. Al Ageel Al Beaiji, “Dengue virus: A global human threat: Review of literature,” Journal of International Society of Preventive and Community Dentistry, vol. 6, no. 1, pp. 1–6, 2016.

W. H. Wang, A. N. Urbina, M. R. Chang, W. Assavalapsakul, P. L. Lu et al., “Dengue hemorrhagic fever – A systemic literature review of current perspectives on pathogenesis, prevention and control,” Journal of Microbiology, Immunology and Infection, vol. 53, no. 6, pp. 963–978, 2020.

Y. Assidiq, “Awal 2022, Demam Berdarah di Situbondo Capai 49 Kasus,” Republika, 2022.

G. D. Prasasti, “Kemenkes: Ada 95.893 Kasus DBD di Indonesia Sepanjang 2020,” Liputan 6, 2020.

G. Saphan, “Kasus DBD Meningkat di Situbondo, Merebak di 15 Kecamatan,” Reportase, 2022.

S. P. Lim, J. H. K. Koh, C. C. Seh, C. W. Liew, A. D. Davidson et al., “A crystal structure of the dengue virus non-structural protein 5 (NS5) polymerase delineates interdomain amino acid residues that enhance its thermostability and de novo initiation activities,” Journal of Biological Chemistry, vol. 288, no. 43, pp. 31105–31114, 2013.

F. Giovannoni, M. F. Ladelfa, M. Monte, D. A. Jans, P. Hemmerich, and C. García, “Dengue Non-structural Protein 5 Polymerase Complexes With Promyelocytic Leukemia Protein (PML) Isoforms III and IV to Disrupt PML-Nuclear Bodies in Infected Cells,” Frontiers in Cellular and Infection Microbiology, vol. 9, no. August, pp. 1–14, 2019.

A. Hidayatullah, W.E. Putra, Sustiprijatno, G.W. Permatasari, W.O. Salma et al., “In Silico Targeting DENV2"s Prefusion Envelope Protein by Several Natural Products" Bioactive Compounds,” Chiang Mai University Journal of Natural Sciences, vol. 20, no. 3, 2021.

V. Galiano, P. Garcia-Valtanen, V. Micol, and J. A. Encinar, “looking for inhibitors of the dengue virus ns5 rna-dependent rna-polymerase using a molecular docking approach,” Drug Design, Development and Therapy, vol. 10, pp. 2163–3181, 2016.

A. Hidayatullah, W.E. Putra, Sustiprijatno, G.W. Permatasari, W.O. Salma et al., “Predicting the possible biological markers as targeted therapy for dengue viral infections,” Malaysian Journal of Biochemistry and Molecular Biology, vol. 24, no. 1, 2021.

I. Manfredonia and D. Incarnato, “Structure and regulation of coronavirus genomes: State-of-the-art and novel insights from SARS-CoV-2 studies,” Biochemical Society Transactions, vol. 49, no. 1, pp. 341–352, 2021.

Y. Zhao, T. S. Soh, J. Zheng, K. W. K. Chan, W. W. Phoo et al., “A Crystal Structure of the Dengue Virus NS5 Protein Reveals a Novel Inter-domain Interface Essential for Protein Flexibility and Virus Replication,” PLoS Pathogens, vol. 11, no. 3, pp. 1–27, 2015.

A. El Sahili and J. Lescar, “Dengue Virus Non-Structural Protein 5.,” Viruses, vol. 9, no. 4, Apr. 2017.

J. E. Fraser, S. M. Rawlinson, C. Wang, D. A. Jans, and K. M. Wagstaff, “Investigating dengue virus nonstructural protein 5 (NS5) nuclear import.,” Methods in molecular biology (Clifton, NJ), vol. 1138, pp. 301–328, 2014.

T. Amemiya, M. M. Gromiha, K. Horimoto, and K. Fukui, “Drug repositioning for dengue haemorrhagic fever by integrating multiple omics analyses,” Scientific Reports, vol. 9, no. 1, pp. 1–13, 2019.

S. Rajapakse, C. Rodrigo, and A. Rajapakse, “Treatment of dengue fever,” Infection and Drug Resistance, vol. 5, no. 1, pp. 103–112, 2012.

K. Panda, K. Alagarasu, P. Patil, M. Agrawal, A. More et al., “In vitro antiviral activity of α-mangostin against dengue virus serotype-2 (Denv-2),” Molecules, vol. 26, no. 10, pp. 1–13, 2021.

A. Widigdyo, E. Widodo, and I. H. Djunaidi, “Extract of Caesalpinia sappan L. as Antibacterial Feed Additive on Intestinal Microflora of Laying Quail,” The Journal of Experimental Life Sciences, vol. 7, no. 1, pp. 7–10, 2017.

A. Naik Bukke, F. Nazneen Hadi, K. S. Babu, and P. C. shankar, “In vitro studies data on anticancer activity of Caesalpinia sappan L. heartwood and leaf extracts on MCF7 and A549 cell lines,” Data in Brief, vol. 19, pp. 868–877, 2018.

D. R. T. Sari, G. C. Krisnamurti, and Y. Bare, “Pemetaan Bioaktivitas Senyawa Metabolit Sekunder Pada Kayu Secang ( Caesalpinia sappan ) Secara In Silico,” Journal Pharmasci (Journal of Pharmacy and Science), vol. 7, no. 1, pp. 21–28, 2022.

G. Bitencourt-Ferreira and W. F. J. de Azevedo, “Molegro Virtual Docker for Docking.,” Methods in molecular biology (Clifton, NJ), vol. 2053, pp. 149–167, 2019.

P. Bhatnagar, G. P. Sreekanth, K. Murali-Krishna, A. Chandele, and R. Sitaraman, “Dengue Virus Non-Structural Protein 5 as a Versatile, Multi-Functional Effector in Host–Pathogen Interactions,” Frontiers in Cellular and Infection Microbiology, vol. 11, no. March, pp. 1–7, 2021.

U. S. F. Tambunan et al., “Modification of S-Adenosyl-l-Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation,” Drug Target Insights, vol. 11, no. C, 2017.

G. C. Krisnamurti, D. R. Sari, and Y. Bare, “Capsaicinoids from Capsicum annuum as an Alternative FabH Inhibitor of Mycobacterium Tuberculosis : In Silico Study Capsaicinoids from Capsicum annuum as an Alternative FabH Inhibitor of Mycobacterium Tuberculosis : In Silico Study,” Makara Journal of Science, vol. 25, no. 4, pp. 195–202, 2021.

Y. Bare, D. R. Sari, Y. T. Rachmad, S. S. N. D. Tiring, A. H. Rophi, and F. A. D. Nugraha, “Prediction Potential Chlorogenic Acid As Inhibitor Ace (In Silico Study),” Bioscience, vol. 3, no. 2, p. 197, 2019.

G. C. Krisnamurti and D. R. T. Sari, “Does Centella Asiatica Have Antiaging Activity in Skincare Products ?,” Atlantis Press, vol. 630, no. Icetech 2021, pp. 240–245, 2022.

Y. Bare, A. D. Kuki, A. H. Rophi, G. C.




DOI: https://doi.org/10.15575/ak.v9i1.17613

Copyright (c) 2022 Dewi Ratih Tirto Sari, Heny Yusuf, Laily Sifaiyah, Nur Dina Camelia, Yohanes Bare

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

CrossrefSINTAGoogle ScholarIndonesia One Search

View My Stats

 

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.