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2017 ; 43
(5
): 521-545
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Iminosugars: Promising therapeutics for influenza infection
#MMPMID27931136
Tyrrell BE
; Sayce AC
; Warfield KL
; Miller JL
; Zitzmann N
Crit Rev Microbiol
2017[Sep]; 43
(5
): 521-545
PMID27931136
show ga
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 ?-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.
|1-Deoxynojirimycin/*analogs & derivatives/therapeutic use
[MESH]
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