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.

Hesperetin blocks poxvirus replication with a low tendency to select for drug‐resistant viral variants

“…This, together with hesperetin‐induced protection in chicken embryos against virulent BPXV, led to the conclusion that hesperetin may potentially be developed as a broad‐spectrum antiviral drug against poxviruses. Previous studies have also identified in vitro antiviral activity of hesperetin against DENV, 28 SARS‐CoV‐2, 25 YFV, 51 CHIKV, 29 ZIKV 29 Sindbis virus, 30 RSV, 31 HSV‐1, 31 and influenza virus 32 . The docking and MD simulations displayed the effect of hesperetin on the viral polymerase of CHIKV, 28 ZIKV, 28 DENV, 28 and RSV 27 .…”

“…[22][23][24] Recent studies have demonstrated the antiviral activity of hesperetin against herpes simplex virus type 1 (HSV-1), poliovirus type 1, parainfluenza virus type 5, respiratory syncytial virus (RSV), influenza A virus, chikungunya virus (CHIKV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yellow fever virus (YFV), Sindbis virus, and dengue virus (DENV). [25][26][27][28][29][30][31][32] In this study, we extended the antiviral efficacy of hesperetin against poxviruses, besides providing insights into its potential mechanisms of action.…”

The Current Landscape of Bioactive Molecules against DENV: A Systematic Review

“…Infections such as dengue could be treated using this method, according to studies at both the transmission and host levels [45]. Within 24 hours, participants in a diferent trial who routinely consumed 2 tablespoons of pawpaw leaf juice daily noticed a rise in their granulocyte count [46].…”

“…Te roots may include a variety of chemical compounds or phytochemicals with a wide range of pharmacological efects [73]. Furthermore, Licorice showed excellent docking characteristics to the protein of dengue [45,74]. It was shown that glycyrrhizin can inhibit Flavivirus procreation at a high nonlethal cytotoxic dose [75].…”

Molecular Dynamics Simulation of Ligands from Anredera cordifolia (Binahong) to the Main Protease (Mpro) of SARS-CoV-2

“…Tropical countries have abundant medicinal plant resources which have yet to be discovered [10][11][12]. Te binahong (Anredera cordifolia) is a plant native to tropical and subtropical South American countries and later brought to Southeast Asia.…”