Molecular Docking Studies of Flavone Derivatives as Inhibitors of RdRP Nora Virus: Computational Insights and Binding Affinity Analysis

ABSTRACT Human viruses with high mutation rates, such as the Nora Virus, pose significant challenges in biomedical research and antiviral drug development, necessitating the exploration of novel therapeutic strategies. The Nora Virus, classified under the genus Phlebovirus within the family Bunyaviridae, relies on RNA-dependent RNA polymerase (RdRP) for viral RNA replication, making RdRP a crucial target for antiviral intervention. In this study, we employed computational approaches, including molecular docking and molecular dynamics simulations, to investigate the inhibitory potential of selected flavone derivatives retrieved from the PubChem database against Nora Virus RdRP (PDB ID: 4LQ3). Ligands were prepared by optimizing their conformations and converting them into appropriate formats for docking with AutoDock Vina, while the protein structure was processed by removing extraneous molecules and defining the active site around key residues such as Cys196 and Cys305. The docking simulations revealed that Apigenin 7-O-Rutinoside exhibited the highest binding affinity with a binding energy of -9.8 kcal/mol, forming multiple hydrogen bonds and extensive hydrophobic interactions with critical amino acids including Glu510, Gly508, and Tyr341. Several other flavonoids, such as 8-Prenylnaringenin and Scutellarein, demonstrated binding energies close to or surpassing that of the standard drug PPND (-8.7 kcal/mol), indicating their potential as effective RdRP inhibitors. The interactions primarily involved key residues, including Glu510 and Trp185, emphasizing their significance in ligand stabilization. These findings align with recent research highlighting flavonoids’ antiviral activity against viral RdRPs. The study underscores the promise of natural flavonoids as lead compounds for developing potent Nora Virus inhibitors, warranting further experimental validation and optimization to establish their therapeutic efficacy. Overall, this research exemplifies the utility of in silico methods in accelerating antiviral drug discovery and the potential of phytochemicals in combating emerging viral threats. Keywords: RdRP Nora Virus, PPND, AutoDock, Molecular Docking, In silico, Flavones.