<p>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. It penetrates into the host cell to transfer its genetic material into the targeted cell followed by replication and establishment of new virus. Thus, the envelope protein can be utilized as the antiviral inhibitor target. 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 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. </p><p><strong>Keywords</strong>: dengue, envelope protein, fusion process, cavity, cyclic peptide, molecular docking, molecular dynamics</p>