Dengue drug discovery: Progress, challenges and outlook.

In the context of the only available vaccine (DENGVAXIA) that was marketed in several countries, but poses higher risks to unexposed individuals, the development of antivirals for dengue virus (DENV), whilst challenging, would bring significant benefits to public health. Here recent progress in the field of DENV drug discovery made in academic laboratories and industry is reviewed. Characteristics of an ideal DENV antiviral molecule, given the specific immunopathology provoked by this acute viral infection, are described. New chemical classes identified from biochemical, biophysical and phenotypic screens that target viral (especially NS4B) and host proteins, offer promising opportunities for further development. In particular, new methodologies ("omics") can accelerate the discovery of much awaited flavivirus specific inhibitors. Challenges and opportunities in lead identification activities as well as the path to clinical development of dengue drugs are discussed. To galvanize DENV drug discovery, collaborative public-public partnerships and open-access resources will greatly benefit both the DENV research community and DENV patients.