Computational screening of flavonoid based inhibitor targeting DENV NS5 methyltransferase

摘要

Dengue virus (DENV) infection has become a global health concern due to its mortality rate in humans. The DENV has infected more than 100 million people around the world. It also caused an endemic in over 100 countries. DENV infection caused breakbone fever and could develop into more severe diseases such as dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS). An effective treatment for DENV infection is indispensable to reduce the mortality rate. Targeting DENV nonstructural protein 5 (NS5) methyltransferase (MTase) could be a potential treatment. The inhibition of NS5-MTase could reduce DENV infection rate. In this research, we used flavonoid compounds from ChEBI Database due to its biological activity as antiviral. The molecular docking simulations of flavonoid database toward NS5-MTase were performed using MOE 2014.09. The docking site of NS5-MTase is determined based on guanosine triphosphate (GTP) binding site. In this study, we obtained ten best ligands from molecular docking simulation which showed a better affinity than GTP. Furthermore, VEGA and FAF-Drugs3 software were also used to predict pharmacological properties of the ten best ligands. Thus, we conclude that based on the docking simulation and pharmacological prediction results, the ligand that has code D341 is the best ligand among others as a NS5-MTase inhibitor.