Abstract

Herpes simplex virus type 1 (HSV-1) is an enveloped DNA virus that is able to establish latent infection. The prevalence of infection is more than 80% among adults, typically causing oral and eye lesions and even life-threatening disease in immunocompromised individuals. The drugs used to treat HSV-1, including viral DNA polymerase inhibitors, are not always effective or well-tolerated by patients, increasing cases of viral resistance to the drugs. Natural compounds, such as polysaccharides, are being investigated as potential drugs to treat viral infections. Crude aqueous and homogeneous alkaline polysaccharide fractions (i.e., SFW and SSFK-10RM, respectively) from the leaves of Stevia rebaudiana (Bertoni) were analyzed to elucidate their anti-HSV-1 action using a plaque reduction assay, cell-cell virus spread analysis, and Western blot of viral glycoprotein expression. The fractions were active in the adsorption and viral penetration phases, with an EC50 of 14 and 22 µg/mL for SSFK-10RM and SFW, respectively. Both polysaccharides neutralized viral particles. The assessment of cell-cell virus spread demonstrated that 50 µg/mL of SSFK-10RM and SFW inhibited the lateral spread of infection by 40% and 70%, respectively. Both fractions inhibited the lateral spread of infection by 100% when tested at a concentration of 100 µg/mL. A partial reduction of the expression of viral glycoproteins gB, gC, and gD was observed during the adsorption phase and after virus penetration in the cell. Complete inhibition was observed when the cells were treated during all stages of infection. Our results suggest that S. rebaudiana polysaccharides are able to both inhibit the early steps of the infection and exert significant antiviral activity after virus entry into the cell by an unknown mechanism. Thus, S. rebaudiana polysaccharides are promising for future research that seeks to treat infections caused by HSV-1 in vivo. Acknowledgements: CNPq, FINEP, CAPES, Fundação Araucária.

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