In silico investigation of artocarpin, cycloarotcarpin, artocarpanone, and cyanomaclurin for Dengue virus inhibitor DEN2 NS2B/NS3 serine protease

Context: Dengue virus (DENV) infection remains a significant global public health challenge that necessitates the development of novel therapeutic strategies. Aims: To investigate compounds isolated from Artocarpus heterophyllus for their potential as inhibitors of the DENV NS2B/NS3 serine protease. Methods: Initially, molecular docking was performed to predict the binding orientation of these flavonoid compounds with the serine protease enzyme. It was followed with pharmacophore, density functional theory (DFT), and ADMET-druglikeness. Results: Results reveal promising interactions between cycloartocarpin and catalytic triad of the NS2B/NS3 protease. This promising candidate displayed the most stable conformation with the lowest gap energy during density functional theory simulation. Additionally, its ADMET profiles confirmed its drug-like properties. Conclusions: Based on these findings, cycloartocarpin was selected as the reference compound for subsequent stages of drug design.