CHAPTER 3: Phenotypic Screening to Discover Inhibitors of Dengue Virus

Dengue is the most prevalent mosquito‐borne viral disease, posing a public health threat to 2.5 billion people worldwide. No clinically approved vaccine or antiviral therapy is currently available. Toward the development of antivirals for the treatment of dengue virus, we have established and applied various cell‐based phenotypic assays to screen large compound libraries. Our screening effort has led to the identification of inhibitors of dengue virus with distinct modes of action. This chapter reviews (i) the overall approaches for anti‐dengue drug discovery, (ii) the current status of cellular phenotypic screening assays for dengue virus and (iii) characterization of three classes of small inhibitors identified from the phenotypic screening. It remains to be determined whether these inhibitors could be further developed into clinical candidates for the treatment of dengue virus infection. However, considering the success of cell‐based screening in the development of antivirals for human immunodeficiency virus and hepatitis C virus, we expect that phenotypic screening should ultimately yield clinical candidates for dengue virus in the near future.