In silico screening of lactic acid bacteria methanolic extract for potential antiviral activity against Japanese encephalitis virus

This study aimed to predict potential interactions between compounds produced by lactic acid bacteria (LAB) and Japanese encephalitis virus (JEV) to identify potential targets for anti-JEV drugs. Virtual screening was conducted by blind docking fourteen selected compounds extracted from 20 LAB strains using Autodock Vina. The interaction between the most commonly produced compounds, namely 3-isobutyl-2,3,6,7,8,8a-hexahydropyrrolo [ 1 , 2 ] pyrazine-1,4-dione (Comp-A), Pyrrolo[1,2- a ]pyrazine-1,4-dione, hexahydro-3-(phenylmethyl)- (Comp-B), and 2,4-ditert-butylphenol (Comp-C), towards the JEV proteins, was investigated through molecular docking supported by other analyses such as ADMET prediction and binding free energy calculation. AutoDock (version 4.2) and Vina predicted the optimal drug binding sites using the number of hydrogen bonds and other important interactions established with the target amino acids and the affinity of the active pockets based on binding energy. The findings demonstrated good affinity of the selected compounds against JEV protein, such as Comp-A (−7.3 kcal/mol), Comp-B (−7.8 kcal/mol), and Comp-C (−8.1 kcal/mol). Molecular dynamics simulations were performed for 100 ns, and a binding affinity weaker than −20 kcal/mol (less negative) suggests that the protein-ligand complex is less active, potentially limiting its contribution to the desired biological activity. In-silico pharmacological evaluation shows that these compounds exhibit the compounds exhibit the binding affinity for drug-like and ADMET properties in micromolar range. Therefore, this analysis anticipated that all three compounds would have antiviral activity against JEV protein, and it is possible to use these findings to direct the development of other antiviral drugs. • Utilized molecular docking and virtual screening to identify potential inhibitors of Japanese Encephalitis Virus (JEV) proteins. • Identified three compounds of lactic acid bacteria metabolites (3-isobutyl-2,3,6,7,8,8a-hexahydropyrrolo [ 1 , 2 ] pyrazine-1,4-dione, Pyrrolo[1,2- a ]pyrazine-1,4-dione, hexahydro-3-(phenylmethyl)-, and 2,4-ditert-butylphenol) with good affinity for JEV proteins. • In-silico pharmacological analysis confirmed favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. • Found these compounds possess favorable drug-like properties, suggesting potential for new antiviral drugs development.