In Silico Study of Compounds in Noni (Morinda citrifolia L.) against Main-Protease in SARS-CoV-2

Samuel Lestyawan; Maitsa Alya Fakhirah; Riska Prasetiawati; Diyani Sovia Anggraeni; Muchtaridi Muchtaridi

doi:10.24198/ijpst.v6i3.58058

In Silico Study of Compounds in Noni (Morinda citrifolia L.) against Main-Protease in SARS-CoV-2

Samuel Lestyawan, Maitsa Alya Fakhirah, Riska Prasetiawati, Diyani Sovia Anggraeni, Muchtaridi Muchtaridi

Abstrak

Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a contagious illness transmitted from person to person. The main protease (Mpro) of SARS-CoV-2 is a promising target for therapeutic intervention. Noni (Morinda citrifolia L.), a plant commonly used in traditional medicine in Indonesia for treating COVID-19, has been investigated for its potential anti-SARS-CoV-2 compounds. However, the specific bioactive compounds targeting SARS-CoV-2 remain unidentified. This study aimed to identify and predict the activity of compounds in Noni against Mpro through pharmacophore modeling, molecular docking, drug-likeness, and pharmacokinetic analysis using LigandScout^®, Discovery Studio Visualizer^®, AutoDock^®, SwissADME, Pre-ADMET, and Toxtree^®. Among the 40 compounds analyzed, quercetin emerged as the most promising candidate, with a pharmacophore fit score of 41.05, a binding energy (ΔG) of -7.79 kcal/mol, and interactions with amino acid residues GLY143A and MET165A, similar to the native ligand. These findings suggest that quercetin from M. citrifolia has the potential to be developed as a novel anti-SARS-CoV-2 therapeutic agent.

Kata Kunci

Anti-SARS CoV-2; main protease; molecular docking; noni; pharmacophore screening

Teks Lengkap:

PDF

Referensi

Kang S, Peng W, Zhu Y, Lu S, Zhou M, Lin W, et al. Recent progress in understanding 2019 novel coronavirus (SARS-CoV-2) associated with human respiratory disease: detection, mechanisms and treatment. International Journal of Antimicrobial Agents. 2020;55(5):105950.

Susilo A, Rumende CM, Pitoyo CW, Santoso WD, Yulianti M, Herikurniawan H, et al. Coronavirus Disease 2019: Tinjauan Literatur Terkini. Jurnal Penyakit Dalam Indonesia. 2020;7(1):45.

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020;395(10223):497-506.

Zhang L, Lin D, Sun X, Curth U, Dorsten C, Sauerhering L, et al. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science. 2020;368(6489): 409-12.

Westberg M, Su Y, Zou X, Huang P, Rustagi A, Garhyan J, et al. An orally bioavailable SARS-CoV-2 main protease inhibitor exhibits improved affinity and reduced sensitivity to mutations. Science Translational Medicine. 2024;16(738).

Li M, Zhang QS, Liu XL, Wang HL, Liu W. Adverse Events Associated with Nirmatrelvir/Ritonavir: A Pharmacovigilance Analysis Based on FAERS. Pharmaceuticals. 2022;15(12): 1455.

Yotsuyanagi H, Ohmagari N, Doi Y. Efficacy and Safety of 5-Day Oral Ensitrelvir for Patients With Mild to Moderate COVID-19. JAMA Network Open. 2024;7(2): e2354991.

Karimi A, Majlesi M, Rafieian-Kopaei M. Herbal versus synthetic drugs; beliefs and facts. Journal of Nephropharmacology. 2015;4(1): 27-30.

Kamata M, Wu RP, An DS, Saxe JP, Damoiseaux R, Phelps RE, et al. Cell-based chemical genetic screen identifies damnacanthal as an inhibitor of HIV-1 Vpr induced cell death. Biochemical and Biophysical Research Communications. 2006;348(3): 1101-6.

Kharaeva Z, Shokarova A, Shomakhova Z, Ibragimova G, Trakhtman P, Trakthman I, et al. Fermented Carica papaya and Morinda citrifolia as Perspective Food Supplements for the Treatment of Post-COVID Symptoms: Randomized Placebo-Controlled Clinical Laboratory Study. Nutrients. 2022;14(11): 2203.

Shaker B, Ahmad S, Lee J, Jung C, Na D. In silico methods and tools for drug discovery. Computers in Biology and Medicine. 2021;137: 104851.

Amin S, Utami F, Maulidya SAI. Virtual Screening of Flavonoid Compounds as A Main Protease Inhibitor for Anti-Sars-Cov-2 Candidates. Indonesian Journal of Pharmaceutical Science and Technology. 2022;9(3):198-209.

Mótyán JA, Mahdi M, Hoffka G, Tőzsér J. Potential Resistance of SARS-CoV-2 Main Protease (Mpro) against Protease Inhibitors: Lessons Learned from HIV-1 Protease. International Journal of Molecular Science. 2022;23(7): 3507.

Zhou Y, Di B, Niu MM. Structure-Based Pharmacophore Design and Virtual Screening for Novel Tubulin Inhibitors with Potential Anticancer Activity. Molecules. 2019;24(17): 3181.

Opo FADM, Alkarim S, Alrefaei GI, et al. Pharmacophore-Model-Based Virtual-Screening Approaches Identified Novel Natural Molecular Candidates for Treating Human Neuroblastoma. Current Issues in Molecular Biology. 2022;44(10): 4838-58.

Nursanti O, Wardani I, Hadisoebroto G. Validasi Penambatan Molekuler (Docking) (Zingiber officinale) dan (Cymbopogon citratus) Sebagai Ligan Aktif Reseptor Pparγ. Jurnal Farmasi Higea. 2022;14(1): 79.

Luo C, Rivkin A, Zhou J, Sandoval JP, Kurihara L, Lucero J, et al. Robust single-cell DNA methylome profiling with snmC-seq2. Nature Communication. 2018;9(1):3824.

Ortiz CLD, Completo GC, Nacario RC, Nellas RB. Potential Inhibitors of Galactofuranosyltransferase 2 (GlfT2): Molecular Docking, 3D-QSAR, and In Silico ADMETox Studies. Scientific Reports. 2019;9(1):17096.

Jin Z, Zhao Y, Sun Y, et al. Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur. Nature Structural & Molecular Biology. 2020;27(6): 529-32.

Lipinski CA, Dominy BW, Feeney PJ. Drug Delivery Reviews Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings. Vol 23.; 1997.

Izzaturahmi AS, Pauziah ASU, Virliana A, Sitinjak GML, Ramadhiany ZZ, Elaine AA, et al. In Silico Study of Licorice (Glycyrrhiza glabra L.) on VEGFR-2 Receptors in Breast Cancer. Indonesian Journal of Biological Pharmacy. 2023;3(3):137-153.

Cramer GM, Ford RA, Hall RL. Estimation of toxic hazard—A decision tree approach. Food and Cosmetics Toxicology. 1976;16(3): 255-76.

Benigni R, Bossa C, Jeliazkova N, Netzeva T, and Worth A. The Benigni/Bossa rulebase for mutagenicity and carcinogenicity–a module of Toxtree. JRC scientific and technical reports 1. 2008;(63): 239.

Kroes R, Renwick AG, Cheeseman M, Kleiner J, Mangelsdorf I, Piersma A, et al. Structure-based thresholds of toxicological concern (TTC): guidance for application to substances present at low levels in the diet. Food and Chemical Toxicology. 2004;42(1):65-83.

Widyasari AD, Nur Ramadhan LOA, Dewi C. Pemodelan Farmakofor dan Skrining Virtual dari Database Senyawa Bahan Alam Sebagai Inhibitor Sars-CoV-2 RNA-dependent RNA Polimerase. Jurnal Pharmacia Mandala Waluya. 2022;1(6):247-57.

Lestari NA, Isrul M, Ramadhan DSF, Fatahu. Skrining Virtual Berbasis Farmakofor Dari Database Bahan Alam Sebagai Inhibitor Alosterik Mutan T790M/C797 EGFR Untuk Penemuan Obat Kanker Paru. Jurnal Pharmacia Mandala Waluya. 2024;3(3):168-86.

Li Q, Shah S. Structure-Based Virtual Screening. Methods in Molecular Biology. 2017:111-24.

Pantsar T, Poso A. Binding Affinity via Docking: Fact and Fiction. Molecules. 2018;23(8): 1899.

Alqahtani MS, Kazi M, Alsenaidy MA, Ahmad MZ. Advances in Oral Drug Delivery. Frontiers of Pharmacology. 2021;12: 618411.

da Silva J, Herrmann SM, Heuser V, Peres W, Marroni NP, Gallego JG, et al. Evaluation of the genotoxic effect of rutin and quercetin by comet assay and micronucleus test. Food and Chemical Toxicology. 2002;40(7):941-947.

DOI: https://doi.org/10.24198/ijpst.v6i3.58058