Cannabidiol Alters Cellular Membranes WithAnImpact On The Zika Virus Replication

MARQUEZ AB; VICENTE J; CASTRO E; VOTA D; RODRIGUEZ VARELA MS; LANZA CASTRONUOVO PA; FUENTES G; PARISE A; ROMORINI L; ALVAREZ D; BUENO C; RAMIREZ C; ALAIMO A; GARCIA CC

Lima

Congreso; PANDENGUE 2023 7th Pan American Dengue Research Network Meeting; 2023

Cannabidiol (CBD), the mainnon-psychoactive cannabinoid of the Cannabis sativaplant,is a powerful antioxidant compound that inrecentyears has increased interest due to causes effectsinawide range of biological functions. Zika virus (ZIKV) isa virus transmitted mainly by the Aedes aegypti mosquitoes, which causes neurological diseases, such as microcephaly and Guillain-Barre syndrome. Inthiswork, we explored the potential antiviral activity of CBD in relevant cellular targets during ZIKVinfections. For this, cell cultures were infected and treated for 48h with CBD (0.6-10 μM). Viral titers of the supernatants were determined and the relative expression of the ZIKV genome was measured by RT- qPCR. The results showed that CBD exhibit a potentantiviral activity against ZIKV in different cell lines with EC50 values ranging from 0.87 to 5.12 μM. In addition, a reduction in the expression of the intracellular ZIKV genome was observed at concentrations of 5 and 10 μM. Furthermore, we evaluated the CBD antiviral activity against dengue, yellow fever and chikungunya arboviruses; the EC50 in Vero cells were 2.02, 2.13 and 4.63 µM, respectively. To study the possible immunomodulatory role of CBD, Huh-7 cells were exposed to 10 μM CBD during 48 h. CBD-treated cells exhibited a significantly IFN-β increased levels, meanwhile, IL-6 and IL-8 were not induced. Due to cell membranes are a key component in all steps of the ZIKV replication cycle, we study the effect of CBD on the membranes. For this, an immunofluorescence assay was performed, in which cell membranes were labeled with wheat germ agglutinin (WGA). We determined that CBD affects cellular membranes due to a higher fluorescence intensity was observed in CBD-treated cells and lowers intracellular cholesterol levels, which were measured by a fluorometric method. Finally, we demonstrate that CBD inhibits other structurally dissimilar viruses, suggesting that this phytochemical has broad-spectrum antiviral activity.