Computational insight into flavonoid-based compound for inhibition activity on SAH-binding site of dengue virus NS5 methyltransferase: Molecular docking and in silico ADME-Tox studies

摘要

Dengue fever is a viral disease that attracts a serious attention worldwide, with almost one-third people in the world is at risk of being struck by dengue fever. Dengue fever is caused by dengue virus (DENV), which mainly transmitted from Aedes aegypti. Non-structural protein 5 (NS5) methyltransferase is a protein that plays a critical role in the proliferation and replication processes of DENV. NS5 methyltransferase has three active sites, SAH, GTP, and RNA-binding site. Thus, these binding sites can be a possible target to block the DENV life cycle and ultimately treat this lethal disease. In this study, we used 1479 flavonoid compounds from ChEBI database to be developed against NS5 methyltransferase in the SAH-binding site. The screening process includes the search of the pharmacological properties of these compounds, resulting 854 compounds in the process. These compounds were carried out into a molecular docking simulation using Molecular Operating Environment (MOE) 2014.09 software. Finally, the remaining compounds were tested with Toxtree and FAF-Drugs3 software to find out the toxicity properties of each flavonoid compounds. In the end, we conclude that anthocyanidin 3,5-diglucoside is the best ligand with the lowest ΔG_(binding) at -55.9826 kcal/mol. Moreover, the pharmacological and toxicity properties of anthocyanidin 3,5-diglucoside also confirmed that this flavonoid compound could be developed as a potential drug candidate to combat dengue fever.