Potential Compounds in Indonesian Herbal Plants using Computational Screening for Inhibitory Activity Against Chikungunya Virus Envelope Protein E2
Abstract
Chikungunya disease, marked by fever, headaches, and severe joint pain, is a significant global health issue, especially in tropical and subtropical regions. Despite its prevalence, there is no specific vaccine or drug for Chikungunya, prompting the need for antiviral drug research. This study targets the envelope protein E2 of the Chikungunya virus (CHIKV) using computational methods to identify potential inhibitory compounds from Indonesian herbal compounds. The CHIKV E2 receptor model was constructed using AlphaFold 2, and molecular docking analyses were performed with herbal compounds from the HerbalDB database using AutoDock-GPU. Molecular dynamics (MD) simulations with Gromacs further assessed ligand-protein interactions. Druggable pocket analysis identified 17 potential ligand-binding regions, with Pocket 0 selected for virtual screening. The virtual screening of 3768 herbal compounds identified 23-Hydroxy-mangiferonic acid (a free energy value of -9.0 kcal/mol) as the most promising candidate due to its high binding affinity and stability in molecular dynamics simulations for 250 ns. MD simulations confirmed the stability and specificity of its interactions with key residues in the targeted pocket. The findings suggest that 23-Hydroxy-mangiferonic acid is a promising therapeutic agent against CHIKV, highlighting the effectiveness of computational methods in antiviral drug discovery. This research lays the groundwork for future experimental validation and development of treatments for Chikungunya infectionsReferences
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