Uji In Silico Aktivitas Senyawa Polifenol Teh Hijau (Camellia sinensis L) terhadap Sars-Cov-2
Abstract
ABSTRACT: COVID-19 is an acute respiratory syndrome disease caused by a new coronavirus known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Polyphenolic compounds Epigallocatechin (EGC), Gallocatechin-3gallate (GCG), Epicatechin (EC) and Epigallocatechin Gallate (EGCG) derived from green tea are compounds that show promise in showing antiviral activity, in vitro showed that EGCG has 85% inhibition against mpro. Mpro is the receptor responsible for SARS-CoV-2. The purpose of this study was to determine the inhibitory activity of polyphenolic compounds from green tea and to observe the interactions that occur in silico. In this study, test was conducted in silico of Mpro receptor activity against polyphenolic compounds using a protein-ligand-based docking method. Starting with the identification of the physicochemical properties of polyphenolic compounds using software ChemBioDraw 2D. then optimized using software Gauss View version 5.0.8 and Gaussian version 09. Followed by a simulation of the docking of polyphenol test compounds against the mpro receptor which has been separated from its natural ligand and has been validated using MGL Toolssoftware 1.5.6which has been equipped with Autodock Tools version 4.2. Epigallocatechin gallate is a compound that has good binding and stability to the Mpro receptor compared to Epigallocatechin (EGC), Gallocatechin-3gallate (GCG), Epicatechin (EC) and its natural ligand (boceprevir) because it has low binding free energy (∆G). namely -9.06 kcal/mol and the inhibition constant (KI) was 0.239 M. Epigallocatechin (EGC), Gallocatechin-3gallate (GCG), Epicatechin (EC) and Epigallocatechin Gallate (EGCG) have a high level of toxicity. predicted in this polyphenol compound is not guaranteed safety supported by parameter cramer rules which shows the category high (Class III).
Keywords: SARS-CoV-2, Mpro, Green tea, Polyphenol
ABSTRAK: COVID-19 merupakan suatu penyakit sindrom pernapasan akut yang disebabkan oleh virus corona baru yang dikenal dengan Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Senyawa Polifenol Epigallocatechin (EGC), Gallocatechin-3gallate (GCG), Epicatechin (EC) dan Epigallocatechin Gallate (EGCG) yang berasal dari teh hijau ini merupakan senyawa yang menjanjikan dalam menunjukkan aktivitas antivirus, secara in vitro menunjukkan bahwa EGCG memiliki 85% penghambatan terhadap Mpro. Mpro merupakan reseptor yang bertanggung jawab yang terdapat pada SARS-CoV-2. Tujuan dari penelitian ini menentukan aktivitas penghambatan senyawa polifenol dari teh hijau serta mengamati interaksi yang terjadi secara in silico. Dalam penelitian ini dilakukan uji in silico aktivitas reseptor Mpro terhadap senyawa polifenol menggunakan metode docking berbasis ligan-protein. Diawali dengan identifikasi sifat fisikokimia pada senyawa polifenol menggunakan software ChemBioDraw 2D. kemudian dioptimasi menggunakan software Gauss View versi 5.0.8 dan Gaussian versi 09. Dilanjutkan dengan simulasi docking senyawa uji polifenol terhadap reseptor mpro yang telah dipisahkan dengan ligan alaminya dan telah di validasi menggunakan software MGL Tools 1.5.6 yang telah dilengkapi dengan Autodock Tools versi 4.2. Epigallocatechin gallate merupakan senyawa yang memiliki ikatan dan stabilitas yang baik terhadap reseptor Mpro dibandingkan dengan senyawa Epigallocatechin (EGC), Gallocatechin-3gallate (GCG), Epicatechin (EC) dan ligan alaminya (boceprevir) karena memiliki energi bebas ikatan (∆G) yang rendah yaitu -9.06 kcal/mol dan konstanta inhibisi (KI) 0,239 µM. Epigallocatechin (EGC), Gallocatechin-3gallate (GCG), Epicatechin (EC) dan Epigallocatechin Gallate (EGCG) memiliki tingkat tokisisitas toksisitas yang tinggi sehingga diprediksi dalam senyawa polifenol ini tidak dijamin keamanannya didukung oleh parameter cramer rules yang menunjukan kategori high (Class III).
Kata kunci: SARS-CoV-2, Mpro, Teh hijau, Polifenol
Keywords
Full Text:
PDFReferences
Bhardwaj, V. K., Singh, R., Sharma, J., Rajendran, V., Purohit, R., & Kumar, S. (2020). Identification of bioactive molecules from tea plant as SARS-CoV-2 mainprotease inhibitors. Journal of Biomolecular Structure and Dynamics, 1–10.
Chan, J. F. W., Yuan, S., Kok, K. H., To, K. K. W., Chu, H., Yang, J., …Yuen, K. Y. (2020). A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: A study of a family cluster. The Lancet, 395, 514–523.
Chandra A.K. and T. Uchimaru. (2002). The O- H bond dissociation energies of substituted phenols and proton affinities of substituted phenoxide ions: A DFT Study, Int. J. Mol. Sci., 3, 407-422.
Gorbalenya, A. E., Baker, S. C., Baric, R. S., de Groot, R. J., Drosten, C.,Gulyaeva, A. A., … Ziebuhr, J. (2020). The species Severe acute respira-tory syndrome-related coronavirus: classifying 2019-nCoV and namingit SARS-CoV-2. Nature Microbiology, 5, 536–544.
Jin, Z., Du, X., Xu, Y., Deng, Y., Liu, M., Zhao, Y., Zhang, B., Li, X., Zhang, L., Peng, C., Duan, Y., Yu, J., Wang, L., Yang, K., Liu, F., Jiang, R., Yang, X., You, T., Liu, X., … Yang, H. (2020). Structure of M(pro) from COVID-19 virus and discovery of its inhibitors. Nature. 582, 289–293.
Kontoyianni, M., McClellan, L.M., Sokol, G.S. (2004). Evaluation of docking performance: comparative data on docking algorithm. Journal of Medicinal Chemistry, 47:558- 565.
Ngo, S. T., Quynh Anh Pham, N., Thi Le, L., Pham, D.-H., & Vu, V. V. (2020). Computational Determination of Potential Inhibitors of SARS-CoV-2 Main Protease. Journal of Chemical Information and Modeling. https://doi.org/10.1021/acs.jcim.0c00491.
Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advance Drug Delivery Reviews
Liu, K., Chen, Y., Lin, R., & Han, K. (2020). Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients. The Journal of Infection, 80, e14–e18.
Ruswanto; Mardhiah; Mardianingrum, R.; & Novitriani, K. (2015). Sintesis dan Studi In Silico Senyawa 3-Nitro-N`-[(Pyridin-4-YL)Carbonyl] Benzohydrazide Seabagai Kandidat ANtituberkulosis. STIKes Bakti Tunas Huasada
Siswandono, dan B. Soekardjo, (2000), Kimia medisinal I dan II, Surabaya: Airlangga University Press. hal 96.
Thi Thanh Hanh, N., Woo, H .-. J., Kang, H .-. K., Nguyen, V., Kim, Y .-. M., Kim, D .-. W., Ahn, S .-. A., Xia, Y., Kim, D,. (2012). Penghambatan yang dimediasi flavonoid dari SARS virus corona seperti protease 3C yang diekspresikan dalam Pichia pastoris. Biotechnol. Lett. 34, 831 - 838.
Xu, L., Liu, J., Lu, M., Yang, D., & Zheng, X. (2020). Liver injury during highly pathogenic human coronavirus infections. Liver International, 40, 998–1004
Azhar Salma Fadhilah, Y Kiki Mulkiya, Kodir Reza Abdul. (2021). Pengaruh Waktu Aging dan Metode Ekstraksi terhadap Aktivitas Antioksidan Black Garlic yang Dibandingkan dengan Bawang Putih (Allium sativum L.). Jurnal Riset Farmasi, 1(1), 16-23.
DOI: http://dx.doi.org/10.29313/.v0i0.30097
