Antiviral activity of the exopolysaccharides produced by Leuconostoc sp. against HSV-1

Introduction: In the current scenario of antiviral research, lactic acid bacteria (LAB) and their derived polymers or polysaccharides are considered potential candidates in antiviral therapy to prevent or treat viral infections in both human and animals with remarkable efficacy and might have significant contribution in medicine and pharmaceutical industries in future. The aim of this work was to study the anti-herpetic activity of exopolysaccharides produced by Leuconostoc sp. Methodology: The strains of the LAB were isolated from fermented homemade vegetables: apples, tomato juice, and sauerkraut. Exopolysaccharides (EPSs) were isolated from the culture fluid. Cytotoxicity and antiherpetic activity of 7 EPSs (15a, 48a, 33a, 43a, 2t, 19s, and 6s) were studied using MTT assay. The influence of EPSs on the herpes simplex virus 1 type (HSV-1) was determined by the virucidal, adsorption and penetration assays. The impact of the EPSs on the cell cycle under a condition of HSV-1 infection was analyzed using flow cytometric analysis of propidium iodide-stained cells. Results: All EPSs demonstrated the minimal cytotoxicity of cells and their CC50 values were >3.5 mg/ml. It was determined, that only EPSs 2t, 19s, and 6s significantly inhibited HSV-1 reproduction; their EC50 value equal to 0.2 and 0.5 mg/ml, and the selectivity index was in the range of 39 – 52. Moreover, their showed virucidal activity when were added to virus 3 h before adsorption reduced HSV-1 infectivity by 86 – 97%. Our studies revealed that these EPSs were able to prevent the HSV-1 attachment to cells and penetration into cells in a different manner, reducing HSV-1 production by 70 – 99 %. Furthermore, the normalization of the number of cells in all phases of the cell cycle compared with the profile of infected cells and the increasing number of cells in G1 phase to 79% compared with the control values of viral infections were determined after using of EPSs. Conclusion: This study presents the first data indicating an enormous potential of using EPSs the genus Leuconostoc sp. for lower or hinder the spread of diseases caused by herpesviruses. Funding: Publications are based on the research provided by the grant support of the State Fund for Fundamental Research (project F83).