Alchemilla Vulgaris Compounds as Inhibitors of HPV 16 E6 Oncoprotein: Quercetin with Promising in Silico Potential
Background: The oncogenic potential of HPV remains a major global public health challenge and various natural therapeutics are being investigated to prevent cancer. The natural components of the Alchemilla vulgaris plant have various anti-inflammatory, antioxidant, antiviral, and anticancer effects. Objective: Therefore, the aim of this study was to bioinformatically examine the potential inhibitory effect of A. vulgaris compounds on the HPV target protein. Methods: The structures of quercetin, catechin, apigenin, luteolin, caffeic and gallic acid were taken from the PubChem database, and the protein structure of the target HPV 16 E6 oncoprotein (PDB ID: 4XR8) from the Protein Data Bank. Virtual screening and docking analysis were performed in AutoDock Vina. Protein-ligand complexes were visualized using Discovery Studio. The molecular dynamics simulation of 4XR8 in complex with quercetin was performed using Desmond. Results: Docking analysis showed that quercetin has the strongest binding affinity with 4XR8 (quercetin -8.9 kcal/mol, apigenin -8.7 kcal/mol, luteolin -8.7 kcal/mol, catechin -8.4 kcal/mol, caffeic acid -7.3 kcal/mol, gallic acid -6.8 kcal/mol). The molecular dynamics simulation results reinforce the stability and strong binding affinity of quercetin within the HPV 16 E6 oncoprotein. Conclusion: Natural components of Alchemilla vulgaris, especially quercetin, have shown promising potential for the treatment of HPV infection and additional in vitro and in vivo studies are needed for their further research.