The aim of this study is to evaluate the possibility to repropose marketed drugs as antiviral ones, based on their ability to reverse the transcriptomic signature of the infected cells. This strategy has to be considered is the context of emerging viral diseases and of increase of resistance to antivirals. Concerning infection by Influenza viruses, two main drugs were identified and evaluated on in vitro and in vivo models: etilefrine and diltiazem. Therefore, it will be assess the efficacy of these two drugs, compared to placebo, to treat severe flu.