

@article {799,
	journal = {Journal of virology},
	volume = {87},
	number = {20},
	year = {2013},
	pages = {11096-11106},
	abstract = {Rotaviruses, nonenveloped viruses presenting a distinctive triple-layered particle architecture enclosing a segmented double-stranded {RNA} genome, exhibit a unique morphogenetic pathway requiring the formation of cytoplasmic inclusion bodies called viroplasms in a process involving the nonstructural viral proteins {NSP5} and {NSP2.} In these structures the concerted packaging and replication of the 11 positive-polarity single-stranded {RNAs} take place to generate the viral double-stranded {RNA} {(dsRNA)} genomic segments. Rotavirus infection is a leading cause of gastroenteritis-associated severe morbidity and mortality in young children, but no effective antiviral therapy exists. Herein we investigate the antirotaviral activity of the thiazolide anti-infective nitazoxanide and reveal a novel mechanism by which thiazolides act against rotaviruses. Nitazoxanide and its active circulating metabolite, tizoxanide, inhibit simian {A/SA11-G3P[2]} and human {Wa-G1P[8]} rotavirus replication in different types of cells with 50\% effective concentrations {(EC50s)} ranging from 0.3 to 2 {\&\#x3BC;g/ml} and 50\% cytotoxic concentrations {(CC50s)} higher than 50 {\&\#x3BC;g/ml.} Thiazolides do not affect virus infectivity, binding, or entry into target cells and do not cause a general inhibition of viral protein expression, whereas they reduce the size and alter the architecture of viroplasms, decreasing rotavirus {dsRNA} formation. As revealed by protein/protein interaction analysis, confocal immunofluorescence microscopy, and viroplasm-like structure formation analysis, thiazolides act by hindering the interaction between the nonstructural proteins {NSP5} and {NSP2.} Altogether the results indicate that thiazolides inhibit rotavirus replication by interfering with viral morphogenesis and may represent a novel class of antiviral drugs effective against rotavirus gastroenteritis.},
	doi = {10.1128/JVI.01213-13},
	url = {http://dx.doi.org/10.1128/JVI.01213-13},
	author = {La Frazia, Simone and Ciucci, Alessandra and Arnoldi, Francesca and Coira, Maurizio and Gianferretti, Patrizia and Angelini, Mara and Belardo, Giuseppe and Burrone, Oscar R and Jean F Rossignol and Santoro, MG}
}
