Assessment of Antiviral Activities of Four Licorice Compounds against Zucchini Yellow Mosaic Virus through Molecular Docking

Abstract This study investigates the molecular docking and binding affinities of four licorice-derived bioactive compounds against 10 proteins of Zucchini yellow mosaic virus (ZYMV), including P1, HC-Pro, P3, 6K1, 6K2, CI, NIa-VPg, NIa-Pro, and NIb. ZYMV is a significant viral pathogen affecting cucurbit crops worldwide, leading to major economic losses. Traditional antiviral strategies have limitations, and bioactive compounds derived from plants have gained attention for their potential to inhibit viral activity. The docking scores reveal that Glycyrrhetic acid and Liquiritin demonstrate the strongest binding, particularly to the P1 target, while Isoliquiritin shows weaker binding. Acyclovir, the control drug, exhibited the least effective binding across all targets. The bonding interactions between the compounds and ZYMV proteins involve a combination of hydrophobic (alkyl, Pi-Alkyl, Pi-Sigma), electrostatic (hydrogen bonds, Pi-Cation, Pi-Anion), and aromatic (Pi-Pi) interactions, each contributing to the stability of the protein-ligand complexes. Glycyrrhetic acid and Liquiritin primarily engage in hydrophobic interactions, enhancing their binding stability, while Isoliquiritin and Glabridin also form electrostatic and aromatic interactions. Some unfavorable interactions, such as donor-donor or acceptor-acceptor bonds, were identified, indicating potential regions for optimization in ligand binding. These findings highlight the promising antiviral potential of licorice-derived compounds, particularly Glycyrrhetic acid and Liquiritin, as inhibitors of ZYMV. The results emphasize the role of non-polar interactions in stabilizing the binding complexes, suggesting these compounds could modulate protein function. The study provides valuable insights for future antiviral drug development, with potential strategies to optimize binding affinity and enhance the efficacy of licorice-derived bioactive compounds in targeting ZYMV.