“Resveratrol y vitaminas: moduladores de la infección por el virus zika”

MARQUEZ AGOSTINA B.; LANZA CASTRONUOVO PRISCILA A.; CASTAÑEDA CATAÑA MAYRA ALEJANDRA; SEPULVEDA CLAUDIA S.; GARCÍA CYBELE C.

Buenos Aires

Congreso; XIII Argentine Conference of Virology 2021; 2021

Zika virus (ZIKV) is an arbovirus belonging to the Flaviviridae family. ZIKV infections have been associated with a wide range of ocular abnormalities, including conjunctivitis, retinal pigmentation changes, optic nerve hypoplasia, hemorrhagic retinopathy, and abnormal retinal vasculature. A primary target of ZIKV is retinal pigment epithelial (RPE) cells, which are key supporting cells for the production of growth factors, recycling of photoreceptor (PR) outer segment-like structures, and transport of nutrients and metabolites between PR and choriocapillaris. Recently, we demonstrated that the Aryl Hydrocarbon Receptor (AHR), a cytoplasmic protein, is a pro-viral factor in ZIKV infections. Furthermore, AHR antagonists have been shown to be effective against ZIKV infection. Moreover, we have determined that resveratrol (RES), a phytochemical, inhibits ZIKV replication. The objective of the present work was to explore the possible interactions of AHR with 12 phytochemicals, including RES by docking and molecular dynamics. It was found that vitamin E, vitamin A, and xanthohumol exhibited binding energies of -13.23, -9.84, and -9.19 kcal/mol, respectively. Based on these results, we selected vitamins A and E to test their potential antiviral effect in vitro. RPE cell cultures were infected and treated with different concentrations of vitamin A. After 48 h, supernatants were collected and viral titers were determined. The results showed that vitamin A reduced 90% of the viral yield at concentrations of 800 µm. On the other hand, vitamin E did not show any effect on viral replication. According to this, and our previous findings, we also evaluated the antiviral activity of combined treatments of vitamin A (800-200 µM) with different concentrations of RES (50-12 µM). RPE cells were infected and treated with several combinations during 48 h, and viral quantification was performed by PFU and RT-PCR assays. The inhibition was significantly higher when both phytochemicals were tested together. In conclusion, this study demonstrated the positive synergy of RES and vitamin A on the inhibition of ZIKV, providing a new perspective for their use in infections caused by ZIKV.