Broad-spectrum agents for flaviviral infections: dengue, Zika and beyond

Abstract

Flaviviruses are a genus within the Flaviviridae family with a single-stranded, positive-sense RNA genome. Many representatives of the genus, such as dengue, West Nile and Zika viruses, are associated with pathogenic effects in humans. Infections with flaviviruses cause symptoms of varying severity, ranging from flu-like illnesses and fevers to potentially lethal haemorrhagic fevers. Neurological complications include encephalitis (for West Nile virus) or microcephaly and Guillain–Barré syndrome (for Zika virus). Vaccine development for humans was successful for some members of the genus, but no specific, pharmacological antiviral agent has reached the market. Drugs with broad-spectrum antiviral activity would be particularly desirable to tackle outbreaks of emerging or neglected flaviviruses. Molecular targets with promising prospects for broad-spectrum relevance include viral proteins, such as the viral protease or polymerase, and host targets exploited by these viruses, including α-glucosidase and mechanisms involved in nucleoside biosynthesis.