In silico, in vitro, and in vivo evaluation of the antiviral potential of glycyrrhizic acid and chitosan nanoparticles against foot and mouth disease virus

Abstract Background Foot-and-mouth disease (FMD) considers as one of the extremely infectious diseases with major economic impact on cloven-hoofed animals globally. The causative agent of the disease, Foot and Mouth Disease Virus (FMDV), comprises seven serotypes designated as; O, A, SAT1, SAT2, SAT3, C, and Asia1. Over the past decades, studies have shown that glycyrrhizic acid, the primary bioactive compound of licorice root, and chitosan, as a biodegradable and biocompatible natural polymer derived from crustacean shells, are potent candidates for inhibition of FMDV activity. The current work evaluated the potential antiviral efficacy of glycyrrhizic acid nanoparticles (GA-NPs) and chitosan nanoparticles (Ch-NPs) against different FMDV serotypes through computational (molecular docking), in vitro and in vivo assays. Materials and methods The study included the use of field isolates from local FMD viral outbreaks (O PanAsia-2, A Iran 05, A Africa 2020, A Africa G IV Egypt 2022, A Venezuela, and SAT2/EGY/2012); Glycyrrhizic acid and chitosan nanoparticles were prepared and characterized; antiviral activity was assessed by molecular docking analysis, BHK-21 cell assays, and experimental animal studies using representative FMDV serotypes. Results Molecular docking showed that GA-NPs exhibited stronger binding affinity toward the FMDV RNA-dependent RNA polymerase (3D pol ) with binding energies of -8.974 kcal/mol while Ch-NPs demonstrated superior binding affinity toward the FMDV VP3 protein with binding energies of -7.173 kcal/mol, respectively. At a concentration of 2 × 10 − 1 mg/ml, both nanoparticles significantly suppressed viral replication, yielding a reduction in viral titers 8, 7.5, 7, 7, 7.5, and 6.5 log₁₀ TCID₅₀/ml for O PanAsia-2, A Iran 05, A Africa 2020, A Africa G IV Egypt 2022, A Venezuela, and SAT2/EGY/2012, respectively which can aid in the disease restriction during outbreaks. Otherwise, at 2 × 10 − 2 mg/ml, treatment markedly reduced viral dissemination in treated guinea pigs, providing protection rates of 66.7%; 44.4%; 66.7%; 100%; and 77.8% and 100% against serotype O; A Iran 05; A Africa 2020; A Africa G IV Egypt 2022; A Venezuela; and SAT2, compared with untreated controls. Conclusion These findings highlighted that GA-NPs and Ch-NPs possess broad-spectrum antiviral activity against six FMDV serotypes, supporting their further development as nanoparticle-based antiviral agents for the control of FMD.