Infecção placentária pelo Zika Vírus: investigação da ação de produtos naturais com atividade antiviral

Abstract

Introduction: The Zika virus (ZIKV) is an emerging arbovirus, which has spread rapidly in recent years and has caused large outbreaks. It originates in Africa and has spread to Asia, Oceania and the Americas, having as its main transmitter the mosquito of the genus Aedes. In 2015, faced with an outbreak in Brazil, it drew the attention of health authorities, where the association of the virus infection with fetal neurological complications began, being supported by studies carried out during the ZIKV outbreaks in Brazil and French Polynesia. . Although ZIKV activity has declined significantly in recent years, the potential for ZIKV introduction and transmission in 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 in the discovery of compounds with antiviral activity. Objective: To characterize the antiviral effect of ethanol extracts obtained from the species Passiflora edulis, Schinus terebinthifolius Raddi, Moringa oleífera and Cocos lucífera, on the response of placental cells exposed to ZIKV. Methods: HTR-8/SVneo cells derived from the first trimester of pregnancy and term placental explants were exposed to the extracts and cell viability was evaluated. The extracts that proved to be viable were exposed to infection by the ZIKV strains in the trophoblast cells and the antiviral potential was analyzed by qRT-PCR and flow cytometry. Faced with the infection and the treatments of the extracts, the cell cycle and production of various cytokines were analyzed. Results: None of the extracts tested decreased the viability of placental explants, on the other hand, only extracts from the seed of Passiflora edulis, fruit of Schinus terebinthifolius Raddi and bark of Schinus terebinthifolius Raddi did not decrease the viability of HTR-8SV/neo cells, therefore being the only ones used in subsequent steps. In the analysis of antiviral activity, all extracts tested were effective in reducing viral load both in HTR-8SV/neo cells and in placental explants, with more promising results with the extract of Passiflora edulis seed. In the production of cytokines, none of the extracts interfered in the modulation of interferons. IL-8 was reduced by the Schinus terebinthifolius Raddi bark extract, while IL-10 was increased by the Schinus terebinthifolius Raddi fruit extract. TNF-α was reduced in the presence of treatments with Schinus terebinthifolius Raddi and Passiflora edulis. Conclusion: The tested extracts are promising sources of compounds with antiviral action against ZIKV, especially the ethanolic extract of Passiflora edulis seed.