In vivo evaluation of antiviral activity of anisomycin against dengue and Zika viruses

Verónica Mara Quintana

Utah State University

Dengue and Zika viruses are public health concern because of their global burden and the lack of vaccines, dengue vaccine is only approved in high dengue endemicity countries, and specific antiviral treatment. In the development of an antiviral agent three main research steps must be accomplished. The first step is to perform in vitro assays, in which the antiviral activity of compounds is evaluated in cell cultures. Those compounds found to be active are further assayed in preclinical in vivo studies using appropriate animal models. Finally, clinical studies in human volunteers should be performed. The aim of my doctoral thesis is the search of novel antiviral molecules against flaviviruses. In vitro studies showed that anisomycin presented a potent and selective antiviral activity against both dengue and Zika viruses. Therefore, the goal of this project is to evaluate the in vivo antiviral activity of anisomycin against dengue and Zika viruses. For that purpose, AG129 mice, which is a suitable model for studying pathogenesis and therapeutic options for both viruses, will be infected with dengue or Zika viruses and treated or not with anisomycin. To assess the efficacy of the compound as antiviral agent we will determine animal survival rate, levels of virus in blood and target organs and production of cytokines usually associated with the symptoms of the disease in treated and untreated mice. The realization of this project is crucial to estimate the potential of anisomycin as a promissory agent to deal with dengue and Zika infections.