  A disease that caused by dengue virus (DENV) has become the major health
problem of the world. Nowadays, no effective treatment is available to overcome
the disease due to the level of dengue virus pathogeneses. A novel treatment
method such as antiviral drug is highly necessary for coping with the dengue
disease. Envelope protein is one of the non-structural proteins of DENV, which
engaged in the viral fusion process. The fusion process is mediated by the
conformational change in the protein structure from dimer to trimer state. The
previous research showed the existing cavity on the dimer structure of the
envelope protein. The existing ligand could get into cavity of the envelope
protein, stabilize the dimer structure or hamper the transition of dimer
protein into trimer. In this fashion, the fusion process can be prevented. The
aim of this research is designing the cyclic peptide with prolin-prolin bond as
fusion inhibitor of DENV envelope protein through molecular docking and
molecular dynamics simulation. The screening of 3,883 cyclic peptides, each of
them connected by prolin-prolin bond, through molecular docking resulted in
five best ligands. The pharmacological and toxicity character of these five
ligands were analised in silico. The result showed that PYRRP was the best
ligand. PAWRP was also chosen as the best ligand because it showed good
affinity with protein cavity. Stability of ligand-protein complex was analyzed
by molecular dynamics simulation. The result showed that PYRRP ligand was able
to support the stability of DENV envelope protein dimer structure at 310 K and
312 K. While PAWRP ligand actively formed complex with the DENV envelope
protein at 310 K compared to 312 K. Thus the PYRRP ligand has a potential to be
developed as DENV fusion inhibitor.
