Molecular Docking and Molecular Dynamics Simulation of Fisetin, Galangin, Hesperetin, Hesperidin, Myricetin, and Naringenin against Polymerase of Dengue Virus

Abstract

Dengue fever is a disease spread by the DENV virus through mosquitoes. This disease is dangerous because there is no specific drug, vaccine, or antiviral against the DENV virus, insisting on drug discovery for dengue fever. RNA-dependent RNA polymerase (RdRp) enzyme in DENV can be a drug target because it has an important role in the virus replication process. In this research, in silico simulations were carried out on bioflavonoid compounds, namely, Fisetin, Galangin, Hesperetin, Hesperidin, Myricetin, and Naringenin with Quercetin as control ligand. QSAR analysis showed that all ligand has the probability to be antiviral and RNA synthesis inhibitor. Docking scores showed that Myricetin, Hesperidin, and Fisetin show strong performance while Hesperidin, Hesperetin, and Naringenin showed strong performance in MM/GBSA. Only Hesperidin showed strong performance in both scorings. Further investigation by ADMET analysis was done to investigate toxicology and pharmacological properties. Our molecular dynamics study through RMSD showed that even though Quercetin does not give good scoring values in both docking score and MM/GBSA, it has robust stable interaction to RdRp. The strong performance of Hesperidin was also validated by protein-ligand contact fraction in 5 ns. Overall, we observed that Hesperidin shows good potential as a DENV-3-RdRp inhibitor in par with Quercetin, although further in vitro study should be conducted.