BackgroundThe emergence of different viral infections calls for the development of new, effective, and safe antiviral drugs.Glycyrrhiza glabrais a well-known herbal remedy possessing antiviral properties.ObjectiveThe objective of our research was to evaluate the effectiveness of a newly developed combination of the probioticsLactobacillus acidophilusandG. glabraroot extract against two viral models, namely the DNA virus Herpes simplex virus-1 (HSV-1) and the RNA virus Vesicular Stomatitis Virus (VSV), with regards to their antiviral properties.MethodologyTo examine the antiviral impacts of various treatments, we employed the MTT assay and real-time PCR methodology.ResultsThe findings of our study indicate that the co-administration ofL. acidophilusandG. glabraresulted in a significant improvement in the survival rate of Vero cells, while also leading to a reduction in the titers of Herpes Simplex Virus Type 1 (HSV-1) and Vesicular Stomatitis Virus (VSV) in comparison to cells that were not treated. Additionally, an investigation was conducted on glycyrrhizin, the primary constituent ofG. glabraextract, utilizing molecular docking techniques. The results indicated that glycyrrhizin exhibited a greater binding energy score for HSV-1 polymerase (− 22.45 kcal/mol) and VSV nucleocapsid (− 19.77 kcal/mol) in comparison to the cocrystallized ligand (− 13.31 and − 11.44 kcal/mol, respectively).ConclusionsThe combination ofL. acidophilusandG. glabraextract can be used to develop a new, natural antiviral agent that is safe and effective.