Influenza virus causes three to five million severe
respiratory infections per year in seasonal epidemics, and sporadic pandemics, three of which occurred in the twentieth century and are a continuing global threat. Currently licensed
antivirals exclusively target the viral
neuraminidase or M2
ion channel, and emerging drug resistance necessitates the development of novel
therapeutics. It is believed that a host-targeted strategy may combat the development of antiviral drug resistance. To this end, a class of molecules known as iminosugars, hydroxylated
carbohydrate mimics with the endocyclic
oxygen atom replaced by a
nitrogen atom, are being investigated for their broad-spectrum
antiviral potential. The influenza virus
glycoproteins,
hemagglutinin and
neuraminidase, are susceptible to inhibition of endoplasmic reticulum α-
glucosidases by certain iminosugars, leading to reduced virion production or infectivity, demonstrated by in vitro and in vivo studies. In some experiments, viral strain-specific effects are observed. Iminosugars may also inhibit other host and virus targets with
antiviral consequences. While investigations of anti-
influenza iminosugar activities have been conducted since the 1980s, recent successes of
nojirimycin derivatives have re-invigorated investigation of the therapeutic potential of iminosugars as orally available, low cytotoxicity, effective anti-
influenza drugs.