MOLECULAR DOCKING OF BIFLAVONOIDS FROM GENUS ARAUCARIA AS DENV NS5 RNA-DEPENDENT RNA POLYMERASE INHIBITOR USING YASARA AND PLANTS PROGRAMS

Abstract

Objective: This study aimed to screen 23 biflavonoids (23 BF) from the Araucaria genus to identify the most promising compound for anti-dengue fever antivirus treatment using in silico techniques with yet another scientific artificial reality application (YASARA) Structure and the Protein-Ligand ANT System (PLANTS) programs. Methods: Predictions of conserved amino acids and potential pockets of the virus dengue NS5 RNA-dependent RNA polymerase (DENV NS5 RdRp) (PDB ID: 5K5M) were examined, while co-crystal ligands were prepared along with 23 biflavonoids. Molecular docking of ligands on the target protein was carried out using the YASARA Structure and PLANTS programs. The interactions were visualized with LigPlot+, Pymol, and Discovery Studio 2021 Client in. pdb format. Results: The results showed that based on the molecular docking of 23 biflavonoids from the Araucaria genus against the selected DENV NS5 RdRp, the top nine compounds with great potential as antiviral drug candidates were identified. Among these compounds, 7,4’,7’’-tri-O-methylagathisflavone (BF3) was distinct as the best choice based on the analysis conducted using the YASARA Structure and PLANTS programs. Other compounds, including 7,4',4'''-tri-O-methylamentoflavone (BF10), 4',4'''-di-O-methylamentoflavone (BF11), 7,4',7'',4'''-tetra-O-methylamentoflavone (BF12), 7''-O-methylamentoflavone (BF13), and 7,7''-di-O-methylamentoflavone (BF14), were selected through the YASARA Structure program, while 7,4',7'',4'''-tetra-O-methylagathisflavone (BF8) and 7''-O-methylrobustaflavone (BF23) were selected from the PLANTS program. All compounds had lower free energy (∆G), dissociation constant (Kd), and docking scores compared to the reference ligand, balapiravir. Hydrogen and hydrophobic bonds were formed with the protein through conserved amino acid residues, the N-pocket, and the catalytic Gly-Asp-Asp (GDD) site. Conclusion: The algorithm differences between the YASARA Structure and PLANTS programs led to the selection of the best compound 7,4',7''-tri-O-methylagathisflavone (BF3) as a candidate antiviral drug for dengue hemorrhagic fever.