In Vitro Antiviral Activity Against Zika Virus From a Natural Product of the Brazilian Brown Seaweed Dictyota menstrualis

Natural products isolated from seaweeds have shown great antiviral potential against numerous viruses such as human type 1 herpes, human immunodeficiency virus, and dengue. Diterpenes produced by the brown seaweeds Dictyota and Canistrocarpus, in particular, have shown antiviral or virucidal activity. Recently, the Zika virus (ZIKV) has become a major public health concern due to its widespread dissemination throughout the Americas. Since no vaccines are available, and no drugs have effectively treated recent cases of infection, our group evaluated products from Dictyota menstrualis for their antiviral potential, alone and in combination with Ribavirin. We first evaluated the compounds' cytotoxicity at high concentrations, and then evaluated the inhibition of ZIKV replication by crude extracts and acetylated crude extracts and their fractions at 20 mu g/mL. The F-6 and FAc-2 fractions, rich in cyclic diterpenes with aldehyde groupings, inhibited ZIKV replication by >74%, with inhibition behaving in a dose-dependent manner and the 50% effective concentration (EC50) values of 2.80 (F-6) and 0.81 (FAc-2) mu g/mL. Regarding the mechanism of action, FAc-2 had strong virucidal potential, and F-6 inhibited viral adsorption. Associating FAc-2 with Ribavirin at suboptimal dosages produced a strong synergistic effect that completely inhibited viral replication. Our results indicate that these natural products have excellent inhibitory potential against ZIKV replication and may be promising for developing affective therapies.