Discovery and design of cyclic peptides as dengue virus inhibitors through structure-based molecular docking

ABSTRACT

OBJECTIVE@#To find potential peptide inhibitors against the NS2B/NS3 protease of DENV which in turn, can inhibit the viral replication inside host cell.@*METHODS@#Cyclic peptides were designed having combination of positively charged amino acids using ChemSketch software and were converted to 3D structures. DENV NS3 protein structure was retrieved from Protein Data Bank (PDB) using PDB Id: 2FOM. DENV NS3 and cylic peptides were docked using MOE software after structural optimization.@*RESULTS@#Through molecular docking it was revealed that most of the peptides bound deeply in the binding pocket of DENV NS2B/NS3 protease an had interactions with catalytic triad. Peptide 2 successfully blocked the catalytic triad of NS2B/NS3 protease. Peptide 1, 4 and 6 also had potential interactions with active residues of the NS2B/NS3 protease while all other peptides were in close contact with the active sites of NS2B/NS3 protease thus, these peptides can serve as a potential drug candidate to stop viral replication.@*CONCLUSIONS@#Thus, it can be concluded from the study that these peptides could serve as important inhibitors to inhibit the viral replication and need further in-vitro investigations to confirm their efficacy.