Placental infection by Zika virus: investigation of natural products with antiviral properties
Natural products, ZIKV, Passiflora edulis, Schinus terebinthifolius Raddi
Introduction: ZIKV is an emerging arbovirus, which has spread rapidly in recent years and caused large outbreaks. It originated from Africa and has spread to Asia, Oceania and the Americas, being transmitted by the mosquito of the genus Aedes. In 2015, an outbreak started in Brazil and it was related the association between ZIKV infection and fetal neurological complications, which was supported by studies carried out during outbreaks in Brazil and in French Polynesia. Although ZIKV activity has significantly decreased in recent years, the potential for ZIKV introduction and transmission into new areas is high and unpredictable. Thus, the development of vaccines and drugs against ZIKV remains a research priority, with natural products being important sources of discovery of compounds with antiviral activity. Objective: To characterize the effect of extracts of natural products on the response of placental cells and tissues exposed to ZIKV. Methods: The toxicity of the extracts was evaluated in explants of chorionic villi from term placenta and the trophoblast cell line HTR-8SV/neo derived from first trimester of pregnancy, by MTT. The effectiveness of viral infection and the effects of extracts was evaluated using two ZIKV strains (MR766 and PE243) and visualized by qRT-PCR, immunofluorescence and flow cytometry. Cell proliferation was assessed by Ki-67 immunolocalization. Results: None of the tested extracts showed toxicity in placental explants, but only the extracts of passion fruit seed, pink pepper fruit and pink pepper peel did not show significant cytotoxicity in HTR-8SV/neo cells, therefore being the only ones used in the steps subsequent ones. In the analysis of antiviral activity, all extracts were effective in reducing the viral load in HTR-8SV/neo cells and in placental explants, with more impactful results with the passion fruit seed extract. In the cell proliferation assay there were no major differences between groups. Conclusion: All these results show that the tested extracts are promising sources of compounds with antiviral action against ZIKV.