Dengue virus nonstructural proteins as small-molecule targets: Advances, challenges, and future directions.

Dengue is no longer confined to tropical and subtropical regions; due to climate change, urbanization, and vector expansion, it has now spread to several Western countries, emerging as a significant global public health threat. A critical unmet need remains for the prevention and treatment of dengue and its complications. In addition to developing vaccines, substantial efforts are underway to discover prophylactic and therapeutic small-molecule inhibitors targeting viral proteins and host factors. This perspective article reviews discovery efforts from the past five years focused on inhibitors of nonstructural (NS) proteins and highlights key directions for future research.