In silico study of 5,7-Dimethoxycoumarin and p-Coumaric acid in Carica papaya Leaves as Dengue Virus Type 2 Protease Inhibitors

Dengue virus is a serious public health issue in tropical and subtropical regions. The global incidence of dengue necessitates the potent antiviral medication for the prevention of proliferation of the virus inside the human body. The DEN2 NS2B/NS3 protease presents in the dengue virus, is an attractive drug target due to its essential role in viral replication, survival, and other cellular activities. In traditional medicine, Carica papaya leaves have been used for the treatment of dengue fever in Sri Lanka, Pakistan, Malaysia. Therefore, phytochemicals present in Carica papaya leaves, have a potential anti-viral activity and can be used as strong drug candidates against the dengue virus. In this investigation, two phytochemical compounds in Carica papaya leaves: 5,7-Dimethoxycoumarin and p-Coumaric acid were selected from the literature and then docked against the DEN2 NS2B/NS3 protease. The compounds showed strong interactions with favorable binding energies in the active site of DEN2 NS2B/NS3 protease. To validate the molecular docking results, the docked ligand-protein complexes were subjected to molecular dynamics simulation along with the apo form of the protein for 30 ns. The molecular dynamics simulation analysis comprising of root mean square deviation and fluctuation, the radius of gyration, hydrogen bonding, DSSP, and MM/PBSA revealed the stability of the apo and complex systems. Interactions formed by these compounds with residues Leu149 and Asn152 are found to be essential for the stability of the ligand-protein complex. The findings revealed that these phytochemical compounds depict the promising results against the DEN2 serotype of the dengue virus and the potential to work as therapeutic drugs. Further experimentation on the proposed compounds is necessary to validate the results and can lead to the development of strong inhibitors with improved activity.