IDENTIFIKASI SENYAWA POTENSIAL DARI Rhoeo spathacea SEBAGAI INHIBITOR MUTAN KatG Mycobacterium tuberculosis SECARA IN SILICO
DOI:
https://doi.org/10.36423/pharmacoscript.v8i1.1800Keywords:
in silico, katG, Rhoeo spathacea, tuberculosisAbstract
Resistensi Mycobacterium tuberculosis terhadap isoniazid (INH) akibat mutasi pada gen katG menjadi tantangan besar dalam penanganan multidrug-resistant tuberculosis (TB-MDR). Mutasi ini menyebabkan penurunan aktivitas enzim katalase-peroksidase, sehingga INH kehilangan efektivitasnya. Oleh karena itu, diperlukan pengembangan agen terapi baru yang mampu berinteraksi dengan mutan katG untuk mengatasi resistensi INH. Penelitian ini bertujuan untuk mengidentifikasi senyawa bioaktif potensial dari nanas kerang (Rhoeo spathacea) sebagai inhibitor mutan katG menggunakan pendekatan komputasi. PASS Online digunakan untuk penyaringan senyawa, dimana senyawa dengan nilai Pa > 0,5 akan dilanjutkan ke studi penambatan molekul dengan AutoDock Vina-PyRx. Pemodelan struktur 3D mutan katG (T271I, G279R, E340Q, dan R373G) dilakukan menggunakan SWISS-MODEL dan hasil interaksi antara ligan dengan protein target dianalisis menggunakan Biovia Discovery Studio. Hasil dari PASS Online menunjukkan empat senyawa (tradecantoside, rutin, peltatoside, dan ferulic acid) memiliki potensi aktivitas antituberculosis dengan nilai Pa > 0,5. Hasil penambatan molekul menunjukkan keempat senyawa memiliki afinitas lebih baik terhadap semua mutan katG dibandingkan dengan INH. Tradecantoside menunjukkan afinitas tertinggi terhadap empat mutan katG kecuali R373G, menjadikannya kandidat potensial untuk pengembangan terapi TB-MDR yang lebih efektif dalam mengatasi resistensi M. tuberculosis.
References
Butnariu, M., Quispe, C., Herrera-Bravo, J., Fernández-Ochoa, Á., Emamzadeh-Yazdi, S., Adetunji, C. O., Memudu, A. E., Otlewska, A., Bogdan, P., Antolak, H., Tamimi, K., Baghalpour, N., Bakhtiyari, J. M., Sen, S., Acharya, K., Segura-Carretero, A., de la Luz Cádiz-Gurrea, M., Lim, S. H. E., Pentea, M., … Sharifi-Rad, J. (2022). A Review on Tradescantia: Phytochemical Constituents, Biological Activities and Health-Promoting Effects. Frontiers in Bioscience - Landmark, 27(6). https://doi.org/10.31083/j.fbl2706197
Chen, D., Oezguen, N., Urvil, P., Ferguson, C., Dann, S. M., & Savidge, T. C. (2016). Regulation of protein-ligand binding affinity by hydrogen bond pairing. Science Advances, 2(3). https://doi.org/10.1126/sciadv.1501240
Depkes RI. (2023). Laporan Program Penanggulangan Tuberkulosis Tahun 2022. Kemenkes RI, 1–147. https://tbindonesia.or.id/pustaka_tbc/laporan-tahunan-program-tbc-2021/
Filimonov, D. A., Lagunin, A. A., Gloriozova, T. A., Rudik, A. V., Druzhilovskii, D. S., Pogodin, P. V., & Poroikov, V. V. (2014). Prediction of the biological activity spectra of organic compounds using the pass online web resource. Chemistry of Heterocyclic Compounds, 50(3), 444–457. https://doi.org/10.1007/s10593-014-1496-1
Fitriyani, Fakih, T. M., & Tjahjono, D. H. (2020). In silico studies of green tea catechins against her-2 receptor in breast cancer. Current Trends in Biotechnology and Pharmacy, 14(5), 194–199. https://doi.org/10.5530/ctbp.2020.4s.23
Grottesi, A., Bešker, N., Emerson, A., Manelfi, C., Beccari, A. R., Frigerio, F., Lindahl, E., Cerchia, C., & Talarico, C. (2020). Computational studies of SARS-CoV-2 3clpro: Insights from md simulations. International Journal of Molecular Sciences, 21(15), 1–18. https://doi.org/10.3390/ijms21155346
Jaiswal, I., Jain, A., Singh, P., Verma, S. K., Prakash, S., Dixit, P., Suryakant, & Singh, M. (2017). Mutations in katG and inhA genes of isoniazid-resistant and -sensitive clinical isolates of Mycobacterium tuberculosis from cases of pulmonary tuberculosis and their association with minimum inhibitory concentration of isoniazid. Clinical Epidemiology and Global Health, 5(3), 143–147. https://doi.org/10.1016/j.cegh.2016.08.008
Kim, Y., Lim, D. J., Song, J. S., Kim, J. A., Lee, B. H., & Son, Y. K. (2022). Identification and Comparison of Bioactive Components of Two Dryopteris sp. Extract Using LC-QTOF-MS. Plants, 11(23), 1–11. https://doi.org/10.3390/plants11233233
Kumar, S., & Jena, L. (2014). Understanding Rifampicin Resistance in Tuberculosis through a Computational Approach. 12(4), 276–282.
Nunn, A. J., Phillips, P. P. J., Meredith, S. K., Chiang, C.-Y., Conradie, F., Dalai, D., van Deun, A., Dat, P.-T., Lan, N., Master, I., Mebrahtu, T., Meressa, D., Moodliar, R., Ngubane, N., Sanders, K., Squire, S. B., Torrea, G., Tsogt, B., & Rusen, I. D. (2019). A Trial of a Shorter Regimen for Rifampin-Resistant Tuberculosis. New England Journal of Medicine, 380(13), 1201–1213. https://doi.org/10.1056/nejmoa1811867
Park, C. H., Yeo, H. J., Baskar, T. B., Park, Y. E., Park, J. S., Lee, S. Y., & Park, S. U. (2019). In vitro antioxidant and antimicrobial properties of flower, leaf, and stem extracts of Korean mint. Antioxidants, 8(3), 1–12. https://doi.org/10.3390/antiox8030075
Purohit, R., Rajendran, V., & Sethumadhavan, R. (2011). Relationship between mutation of serine residue at 315th position in M. tuberculosis catalase-peroxidase enzyme and Isoniazid susceptibility: An in silico analysis. Journal of Molecular Modeling, 17(4), 869–877. https://doi.org/10.1007/s00894-010-0785-6
RA Linda, Z. A. (2020). FREKUENSI MUTASI GEN katG S315T M . Tuberculosis PADA PASIEN MDR TB DI SUMATERA SELATAN RA Linda Andriani , Zen Ahmad. 7(2).
Radji, M., Kurniati, M., & Kiranasari, A. (2015). Comparative antimycobacterial activity of some Indonesian medicinal plants against multi-drug resistant Mycobacterium tuberculosis. Journal of Applied Pharmaceutical Science, 5(1), 019–022. https://doi.org/10.7324/JAPS.2015.50104
Sasikumar, K., Ghosh, A. R., & Dusthackeer, A. (2018). Antimycobacterial potentials of quercetin and rutin against Mycobacterium tuberculosis H37Rv. 3 Biotech, 8(10), 1–6. https://doi.org/10.1007/s13205-018-1450-5
Saudale, F. Z. (2020). Pemodelan Homologi Komparatif Struktur 3d Protein dalam Desain dan Pengembangan Obat. Al-Kimia, 8(1), 93–103. https://doi.org/10.24252/al-kimia.v8i1.9463
Srivastava, G., Tripathi, S., Kumar, A., & Sharma, A. (2017). Molecular investigation of active binding site of isoniazid (INH) and insight into resistance mechanism of S315T-MtKatG in Mycobacterium tuberculosis. Tuberculosis, 105, 18–27. https://doi.org/10.1016/j.tube.2017.04.002
Takawira, F. T., Mandishora, R. S. D., Dhlamini, Z., Munemo, E., & Stray-Pedersen, B. (2017). Mutations in rpoB and katG genes of multidrug resistant mycobacterium tuberculosis undetectable using genotyping diagnostic methods. Pan African Medical Journal, 27. https://doi.org/10.11604/pamj.2017.27.145.10883
Tan, J. B. L., Lim, Y. Y., & Lee, S. M. (2015). Antioxidant and antibacterial activity of Rhoeo spathacea (Swartz) Stearn leaves. Journal of Food Science and Technology, 52(4), 2394–2400. https://doi.org/10.1007/s13197-013-1236-z
Torres, J. N., Paul, L. V., Rodwell, T. C., Victor, T. C., Amallraja, A. M., Elghraoui, A., Goodmanson, A. P., Ramirez-Busby, S. M., Chawla, A., Zadorozhny, V., Streicher, E. M., Sirgel, F. A., Catanzaro, D., Rodrigues, C., Gler, M. T., Crudu, V., Catanzaro, A., & Valafar, F. (2015). Novel katG mutations causing isoniazid resistance in clinical M. Tuberculosis isolates. Emerging Microbes and Infections, 4(7), e42. https://doi.org/10.1038/emi.2015.42
Tseng, S. T., Tai, C. H., Li, C. R., Lin, C. F., & Shi, Z. Y. (2015). The mutations of katG and inhA genes of isoniazid-resistant Mycobacterium tuberculosis isolates in Taiwan. Journal of Microbiology, Immunology and Infection, 48(3), 249–255. https://doi.org/10.1016/j.jmii.2013.08.018
Umar, F. F., Husain, D. R., Hatta, M. M., Natzir, R. R., Sjahril, R. S., Dwiyanti, R. R., Junita, A. R., & Primaguna, M. R. (2020). Molecular characterisation of mutations associated with resistance to first- and second-line drugs among Indonesian patients with tuberculosis. Journal of Taibah University Medical Sciences, 15(1), 54–58. https://doi.org/10.1016/j.jtumed.2019.12.003
Unissa, A. N., Selvakumar, N., Narayanan, S., Suganthi, C., & Hanna, L. E. (2015). Investigation of Ser315 substitutions within katG gene in isoniazid-resistant clinical isolates of mycobacterium tuberculosis from South India. BioMed Research International, 2015. https://doi.org/10.1155/2015/257983
Waterhouse, A., Bertoni, M., Bienert, S., Studer, G., Tauriello, G., Gumienny, R., Heer, F. T., Beer, T. A. P. De, Rempfer, C., Bordoli, L., Lepore, R., & Schwede, T. (2018). SWISS-MODEL : homology modelling of protein structures and complexes. Nucleic Acids Research, 46, 296–303. https://doi.org/10.1093/nar/gky427
Wiederstein, M., & Sippl, M. J. (2007). ProSA-web : interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Research, 35, 407–410. https://doi.org/10.1093/nar/gkm290
World Health Organization. (2023). Report 2023. In January (Issue March).
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