In vivo antiviral activity of two newly developed compounds reduces the harmful effects of ZIKV in chicken embryos.

Zika virus (ZIKV) is a human teratogen responsible for Congenital ZIKV Syndrome (CZS). This syndrome is characterized by a set of congenital anomalies markedly by microcephaly in newborns. To date, there is no fully approved medicine or vaccine that can prevent or minimize the harmful effects caused by ZIKV on embryonic development. Recently, two newly developed compounds, TH5487 and TH6744, have been shown to be antiviral and to reduce the toxic effects of ZIKV on brain organoids. Here, using a combination of analyses, we evaluated the teratogenic and anti-ZIKV activities of TH5487 and TH6744 using chicken embryos as experimental models. First, a range of concentrations of both compounds were applied to the embryos, and survival and malformation rates were assessed. The highest nontoxic dose was subsequently used to test the ability of the compounds to reduce the effects of ZIKV on chicken brain development. We found that both compounds are nonteratogenic, not affecting the survival, development or growth of chicken embryos at any tested concentration. In addition, embryos exposed to ZIKV and later exposed to the compounds presented head sizes comparable to those of controls (without virus), indicating the in vivo antiviral capacity of TH5487 and TH6744. In conclusion, the two compounds tested were nonteratogenic and presented antiviral potential, minimizing the effects caused by ZIKV on brain development. Further tests with other species should be performed to explore the development of these compounds.