Despite a century of scientific advances, infectious diseases are still one of the main causes of death worldwide. Among mosquito-transmitted diseases, those caused by the dengue fever (DEN) virus, pose the most serious public health hazard. Although vaccine immunization is a better choice for the prevention of disease, it has encountered great difficulties in the case of DEN because of the existence of four different viral subtypes that do not confer cross-immunity. Screening for potential anti-viral drugs against DEN virus infection is the best alternative while an effective, safe vaccine is not developed. Therefore, our major goal is to identify interaction partners between viral and cellular macromolecules that suggest targets for rational drug design against the DEN virus from the determination of their 3-D structures. We aim to search for potential inhibitors that prevent DEN virus fusion with cellular membrane by NMR. Other important targets are macromolecules involved in the DEN replication process. However, their limitation as potential candidates is the very few information about their identity and function in vivo. So, we aim to characterize function and structure of the NS proteins and the UTRs of the DEN virus, in free state and bound to their partners. We are currently determining the 3D structure of dengue virus fusion peptide both free in solution and bound to detergent micelles at fusiogenic condition by nuclear magnetic resonance and small angle X-ray scattering. We are also working together with the Rio proteomic network attempting to identify proteins that are differentially expressed in the culture liver cells infected with dengue virus relatively to non-infected cells.