Structural Analysis and Molecular Modeling Studies of Fatty Acids and Peptides Binding with NS2B/NS3 Dengue Protease

Dengue is one of the life threatening diseases. The non-structural protein3 (NS3) is the virus protease essential for the polyprotein processing which requires the presence of ~40 residue hydrophilic domain from NS2B cofactor for its optimal catalytic activity. The complex of NS2B/NS3 active protease is categorized as a trypsin like protease. Design of peptide based drugs towards the protease is one of the widely accepted strategies against this virus. The conformation adopted by NS2B plays an important role in the activity of the protease and also in the binding of the substrate. We have attempted to design peptides against NS2B/NS3 through various approaches. The ligands were selected from different sources, from peptides isolated from edible fishes to natural compounds isolated from papaya leaves. The binding mode of the ligands was studied with respect to different conformations of the protease.