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Crit Rev Microbiol ; 43(5): 521-545, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27931136

RESUMEN

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.


Asunto(s)
1-Desoxinojirimicina/análogos & derivados , Antivirales/uso terapéutico , Inhibidores de Glicósido Hidrolasas/uso terapéutico , Gripe Humana/tratamiento farmacológico , 1-Desoxinojirimicina/uso terapéutico , Animales , Farmacorresistencia Viral , Retículo Endoplásmico/enzimología , Retículo Endoplásmico/metabolismo , Glicosilación , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Humanos , Subtipo H1N1 del Virus de la Influenza A/metabolismo , Gripe Humana/virología , Ratones , Neuraminidasa/metabolismo , alfa-Glucosidasas/metabolismo
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