Small molecule drug discovery for Ebola virus disease

Known for its widespread outbreaks, including the 2013–2016 epidemic that infected almost 29 000 individuals and resulted in approximately 11 300 deaths, Ebola virus (EBOV) and related filoviruses remain a current threat as consecutive filoviral outbreaks have occurred between 2021 through 2025. Due to high fatality rates of 40–90% among infected individuals, researchers have invested significant efforts to discover effective treatments for Ebola virus disease. Small molecules hold great potential for treating Ebola virus disease because they can target various stages of the filoviral life cycle, such as entry, transcription, replication, and egress; however, the FDA has not yet approved any small molecule treatments for EBOV. In this review, we report both historic and recent progress in the discovery of small molecule drugs for EBOV.