New developments in flavivirus drug discovery

ABSTRACT

Introduction: Flaviviruses are major causes of infectious disease. The vast global, social and economic impact due to morbidity and mortality associated with diseases caused by these viruses urgently demands effective therapeutic interventions. There is currently no specific antiviral therapy available for the effective clinical treatment of infections by any of the flaviviridae. Development of more effective vaccines and antiviral agents for the prevention and treatment of most flavivirus infections remains a clear public health priority in the 21st century.

Areas covered: This review describes some of the recent discoveries in the field of flavivirus inhibitor development, with a particular focus on targeting viral proteins. Emphasis is placed on the advances published during the 2012–2015 period.

Expert opinion: The field of drug discovery targeting viral proteins has progressed slowly in recent years. New information, particularly on structures, location and mechanisms of action of established protein targets have been reported. There have also been studies on repurposing known drugs as templates for targeting flavivirus proteins and these hits could be promising templates for developing new more potent inhibitors. Further research should be conducted to improve in vitro assays that better reflect the conditions found in cellular environments.

KEYWORDS:

• Antiviral
• dengue
• flavivirus
• inhibitor
• nucleoside
• peptide
• small molecule

Article highlights

• Flaviviruses are important global human pathogens that threaten the lives of millions of people every year.

• There is currently no clinically approved antiviral drug therapy against any of these flaviviral infections.

• Viral entry and viral protein targets such as polymerases and proteases continue to attract most attention for development of antiviral therapeutics against flaviviruses.

• Known drugs for other indications are being examined as templates for flavivirus therapies, there is value in developing novel uses for existing drugs.

• There is a need for improvements in in vitro infection assays and animal models to better mimic disease pathogenesis in humans for successful drug development in the future.

• As flavivirus drugs are needed in most resource-poor countries, not-for-profit initiatives are crucial to facilitating drug development.

Acknowledgements

The author thanks Prof David Fairlie and Dr Martin Stoermer (University of Queensland) for his suggestions.

Financial and competing interests disclosure

The National Health and Medical Research Council provided funding for this work under grant APP1025883 at the University of Queensland. The author has no other 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 apart from those disclosed.