Iminosugars: Promising therapeutics for influenza infection. (3rd September 2017)

• Record Type: Journal Article
• Authors: Tyrrell, Beatrice Ellen; Sayce, Andrew Cameron; Warfield, Kelly Lyn; Miller, Joanna Louise; Zitzmann, Nicole
• Is Part Of: Critical reviews in microbiology. Volume 43:Number 5(2017)
• Page Start: 521
• Page End: 545
• Publication Date: 2017-09-03
• Subjects: Influenza -- iminosugars -- N-glycosylation -- hemagglutinin -- neuraminidase; Microbiology -- Periodicals; Microbiology -- Periodicals; Review Literature -- Periodicals; 579
• DOI: 10.1080/1040841X.2016.1242868
• Languages: English
• ISSNs: 1040-841X

Abstract

Abstract: 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.