Antiviral effect of ursolic acid in in vitro Rotavirus infection mediated by the interference in the viroplasm biogenesis

MARÍA CECILIA GIMENEZ; JULIETA THOMÉ CHAPINI; DELGUI, LAURA R.; COLOMBO, M.I.

Simposio; II Simposio Internacional de Medicina Traslacional; 2019

Rotavirus (RV) is one of the most important pathogens causing severe gastroenteritis, which remains to be a leading cause of morbidity and mortality in infants and children worldwide. Since no specific treatment is currently available, this work was intended to explore the ursolic acid (UA), a natural triterpenoid with extensively studied biological properties, as a possible anti-RV agent in vitro.A dose-dependent anti-RV activity was observed when UA was incorporated at all stages of RV replication cycle, which was not due to a direct effect of UA over the viral particles. The inhibiting effect of UA was demonstrated by a significant decrease in the level of the main RV proteins (VP6 and VP7) and the viral progeny titer. Toward dissecting the replication step targeted by the UA, we separately analysed the early and late stages of infection. We observed a significant decrease in i) the level of VP6 and NSP2 proteins; ii) the number and size of viroplasms; and iii) the viral progeny titer when UA was included in the early stages of the replication cycle. We analyzed the mechanism of action and observed that UA induces the degradation of lipids causing a significant reduction in the number and size of lipid droplets in UA-treated cells, directly affecting the viroplasm formation and the RV replication cycle.Altogether, our results describe a robust anti-RV effect mainly interfering with the viroplasm formation, pointing the UA as an attractive alternative therapy.