DESIGNING CYCLIC PENTAPEPTIDE AS INHIBITOR RNA-DEPENDENT RNA POLYMERASE DENGUE VIRUS BY MOLECULAR DOCKING
Rna-Dependent Rna Polymerase (RdRp) is one of dengue proteins that can be used as an antiviral potential target, because human cell avoid this function. This enzyme is responsible in the replication process. Some studies in developing the inhibitor for it’s binding site were based on nucleoside analog (NI), but maybe it can caused resistant strain. In this study, we design peptide as the inhibitor because of its high activity and specify. 216 cyclic pentapeptide inhibitors have already designed in this study. Two amino acids (cys) were put in the end of the structure to make a disulfide bridge and six amino acids (asp, glu, ser, lys, arg, and gly) were selected randomize as the three main amino acids, so they can bind to the binding site. The interaction study of ligand and receptor was performed by MOE 2008.10. The result showed that cyclic pentapeptide SDE and EKE were selected as the potential inhibitor with free energy binding -25.9690 kJ/mol and -37.6361 kJ/mol, respectively. Several modes of weak interactions were observed between cyclic pentapeptide SDE and cyclic pentapeptide EKE to the binding site of DEN-3 NS5 RdRp. Therefore, this cyclic pentapeptide could be proposed as a potential inhibitor to the NS5 RdRp activities of dengue virus type 3.
Keywords. Dengue virus, inhibitor, docking, DEN-3 NS5 RdRp, peptide