Pediatric Drug Nitazoxanide: A Potential Choice for Control of Zika

Cao, Rui-Yuan; Xu, Yong-fen; Zhang, Tian-Hong; Yang, Jing-Jing; Yuan, Ye; Hao, Pei; Shi, Yi; Zhong, Jin; Zhong, Wu

The pretreatment of the cells with the compounds for 4, 8, 12, and 24 hours did not inhibit the ZIKV infection, further confirming that the compounds do not act on the ZIKV entry (Supplementary Figure 4) . In addition, we have performed a time-of-addition experiment using a high MOI. As shown in Figure 2D , addition of the compounds at 24 hours after the ZIKV infection at a MOI of 2 still potently inhibits virus infection, strongly suggesting that the drugs are capable of inhibiting established ZIKV infection, likely at a step of virus genome replication. A (H7N9). It is also reported to inhibit the replication of a broad range of other RNA and DNA viruses including respiratory syncytial virus, parainfluenza, coronavirus, rotavirus, norovirus, hepatitis B, hepatitis C, dengue, yellow fever, Japanese encephalitis virus, and human immunodeficiency virus [12] . Clinical trials have indicated its potential role in treating rotavirus and norovirus gastroenteritis, chronic hepatitis B, chronic hepatitis C, and influenza. It is suggested that nitazoxanide may inhibit virus infection by regulating the host responses [9] . The specific mechanism may be associated with its depleting intracellular Ca 2+ stores [13] . Thiazolides were also reported to inhibit the replication of H1N1 and different other strains of influenza A virus by selectively blocking the maturation of the viral hemagglutinin at a stage preceding resistance to endoglycosidase H digestion [14] . Our results indicate that nitazoxanide inhibits ZIKV infection by targeting the postattachment step, most likely virus genome replication. Perhaps, it also inhibits ZIKV replication by depleting intracellular Ca 2+ stores like bovine viral diarrhoea virus; however, novel mechanisms cannot be excluded in this setting, and further investigation needs to be performed.