To strengthen EU's ability to fight DENV and WNV epidemic and pandemic threats and elaborate effective emergency plans. The project is based on three pillars: 1) clinical investigation of host factors related to severe disease, 2) therapeutic development (i.e. host-viral protein binding inhibitors) and 3) One-Health-based surveillance of the infections. Open science practices will guarantee quality, efficiency of the research and maximise the impact of the project. The declaration of interest in the InFlaMe project of a company, world leader in the field, supports the thrustable of the network and the impact of the project’s expected outcomes. The project’s tasks will proactively be addressed in 7 sounding work packages and will go beyond the state-of-the-art. The partners have outstanding experience in all the aspects of the project, collaborated previously and working together on emerging flaviviral infections. The team includes Fondazione IRCCS Policlinico San Matteo as coordinator (IT; Fausto Baldanti), the National Institute of Molecular Genetics (IT; Renata Grifantini, Antonio Lanzavecchia and Raffaele De Francesco), Pasteur Institute (FR; Jouvenet Nolween), CIC Biogune Institute (ES; Jesus Jimenos-Barberez and Nicola Abrescia), University of Florence (IT; Cristina Nativi), Centro Nazionale per le Ricerche (IT; Giovanni Maga and Paolo Mazzetti ), Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna (IT; Ana Maria Moreno Martin), IMAGINE Institute (FR; Jean Laurent Casanova and Shen-Ying Zhang,), University of Vienna (AT; Judith Aberle and Karin Stiasny) and University of Masaryk (Daniel Ruzek). This truly complementary and collaborating network has a robust know-how in diagnosis of flaviviruses in humans and animals, on host-pathogen interaction and drug discovery.