Bioactive Phytochemicals as Inhibitors against Dengue virus protein NS-5 Methyltransferase: In Silico Molecular Docking Approach

Bioactive Phytochemicals as Inhibitors against Dengue virus protein NS-5 Methyltransferase

Abstract

Background: Dengue fever has emerged globally as a major public health concern since the last decade due to its high morbidity and mortalities. Phytochemicals play an important role as antivirus inhibitors against virus induced diseases. This study aims to an in silico identification of phytochemicals as potential inhibitors against dengue viral protein NS5 methyltransferase (NS5-MTase), an enzyme critical to dengue RNA replication (PDB ID 5E9Q). It is an attractive drug target for new antiviral medicines. Materials and Methods: AutoDock1.5.6 was used for prediction of binding interaction between the ligands and the receptor protein. Lipnki's rule of five was also assed for molecular properties of ligands. Discovery studio software was used for visualisation of 2D and 3D interactions. The five phytochemicals selected for this study were rutin, curcumin, D-camphor, quercetin and amentoflavone. Results:These phytochemicals were docked with NC-5 MTase using the AutoDock and exhibited hydrogen bonding interactions at binding pocket. Among the phytochemicals i.e. rutin (-4.59 kcal/mol), curcumin (-5.20 kcal/mol), D-camphore (-5.21 kcal/mol), quercetin (-5.41 kcal/mol), amentoflavone displayed the highest docking score -6.05 kcal/mol with the most hydrogen bonds (eight) at the active site of the target protein. Hydrogen bonding interactions between phytochemical compounds and NS5-MTase's active binding pocket suggest that phytochemicals may block substrate binding or disrupt its catalytic mechanism in order to inhibit enzyme activity. Conclusion: These result suggested that studied phytochemicals might have antiviral binding affinity with the NS5-methyltransferase enzyme activity and amentoflavone was most potential antiviral  NS-5 methyltransferase inhibitor.  This study needs an experimental validation of these  phytochemicals for the development of dengue antiviral therapies.