Repurposing Mitragynine as Anti-SARS-CoV-2 Agent Evidenced by In Silico Predictive Approach

• Published in: Malaysian Journal of Fundamental and Applied Sciences
• Main Author: Tap F.M.; Zakaria N.H.; Majid F.A.A.; Huq A.K.M.M.; Jamal J.A.
• Format: Article
• Language: English
• Published: Penerbit UTM Press 2022
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85145931929&doi=10.11113%2fmjfas.v18n6.2637&partnerID=40&md5=99418f1994dd63effbb8b4dd3e3827ce

The outbreak of a new coronavirus strain (SARS-CoV-2) calls for the development of treatment approaches to address the disease. Therefore, an in silico study was conducted to evaluate druggability capacity of mitragynine, a natural indole alkaloid compound, using adsorption, distribution, metabolism, and excretion (ADME) prediction and molecular docking simulation to the region binding domain of severe acute respiratory coronavirus 2 (SARS-CoV-2 RBD). The pharmacodynamics of mitragynine were evaluated for its druggability using SwissADME software, and molecular docking simulation was performed using AutoDock software, using SARS-CoV-2 RBD (PDB ID: 6M0J) as the protein target retrieved from Protein Data Bank (PDB). ADME predicted that this compound has excellent druggability, transport properties, and pharmacokinetics, following Lipinski's rule of five. Mitragynine was also nonmutagenic based on the AMES toxicity test. No PAINS alert was observed and the synthetic acceptability score was 4.49, suggesting a moderately synthesised compound. Through the molecular docking approach, mitragynine successfully docked the binding site of SARS-CoV-2 RBD with a binding energy of -6.3kcal/mol and formed hydrogen bonds with the residue N501, which is one of the residues at the binding site of RBD. These findings, together with other therapeutic qualities of mitragynine warrant more research into molecular dynamics, in vitro, and in vivo studies in COVID-19 therapy. © 2022 Malaysian Journal of Fundamental and Applied Sciences.