New avenues for therapeutic discovery against West Nile virus

ABSTRACT

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:

• West Nile virus
• Antiviral drug
• drug discovery
• Flavivirus
• Therapeutic antibody
• Vaccine
• siRNA
• NS3
• NS5
• Zika virus

Article highlights

• In the recent years, new epidemic strains of West Nile virus (WNV) have emerged and caused large human outbreaks of neuroinvasive disease.

• No antiviral drugs have been licensed for WNV and other flavivirus infections in humans.

• Anti-WNV drug candidates that have been developed so far are still at the preclinical stage and most have been tested only in vitro.

• As in the case of HIV and HCV polymerases and proteases, targeting conserved enzymatic motifs in WNV NS3 protease and NS5 polymerase appears the most promising therapeutic strategy.

• Targeting host factors required for viral infection and replication and modulation of host innate antiviral response might lead to the development of compounds with broad-spectrum antiviral activity.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Referee Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.