Introduction: West Nile virus (WNV) is a neurotropic mosquito-borne flavivirus, which is endemic in many countries, especially in Europe and in North America, where the virus has increased its activity in the recent years. No vaccines nor antiviral drugs are available for the prevention and treatment of WNV infection in humans.Areas covered: This review article describes viral and host targets that have been addressed by anti-WNV drug discovery studies and summarizes the most relevant anti-WNV candidate compounds identified so far, focusing on those showing antiviral efficacy in in vivo models and broad-spectrum anti-flavivirus activity.Expert opinion: The most promising anti-WNV drug candidates target conserved enzymatic motifs in viral NS3 protease and NS5 polymerase and are effective against different flaviviruses. Targeting host factors required for viral infection and replication and modulation of host innate antiviral response are also promising approaches, which may lead to the development of compounds with broad-spectrum antiviral activity, a desirable feature for an antiviral drug.
Keywords: Antiviral drug; Flavivirus; NS3; NS5; Therapeutic antibody; Vaccine; West Nile virus; Zika virus; drug discovery; siRNA.