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Norovirus: Targets and tools in antiviral drug discovery

机译：诺如病毒：抗病毒药物发现的目标和工具

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The development of antiviral strategies to treat or prevent norovirus infections is a pressing matter. Noroviruses are the number 1 cause of acute gastroenteritis, of foodborne illness, of sporadic gastroenteritis in all age groups and of severe acute gastroenteritis in children less than 5 years old seeking medical assistance [USA/CDC]. In developing countries, noroviruses are linked to significant mortality (～200 000 children <5 years old). Noroviruses are a major culprit for the closure of hospital wards, and associated with increased hospitalization and mortality among the elderly. Transplant patients have significant risk of acquiring persistent norovirus gastroenteritis. Control and prevention strategies are limited to the use of disinfectants and hand sanitizers, whose efficacy is frequently insufficient. Hence, there is an ample need for antiviral treatment and prophylaxis of norovirus infections. The fact that only a handful of inhibitors of norovirus replication have been reported can largely be attributable to the hampering inability to cultivate human noroviruses in cell culture. The Norwalk replicon-bearing cells and the murine norovirus-infected cell lines are the available models to assess in vitro antiviral activity of compounds. Human noroviruses have been shown to replicate (to some extent) in mice, calves, gnotobiotic pigs, and chimpanzees. Infection of interferon-deficient mice with the murine norovirus results in virus-induced diarrhea. Here we review recent developments in understanding which norovirus proteins or host cell factors may serve as targets for inhibition of viral replication. Given the recent advances, significant progress in the search for antiviral strategies against norovirus infections is expected in the upcoming years.
机译：开发治疗或预防诺如病毒感染的抗病毒策略已成为当务之急。诺如病毒是导致所有年龄段的急性胃肠炎，食源性疾病，偶发性胃肠炎以及5岁以下儿童寻求医疗救助的严重急性胃肠炎的首要原因[USA / CDC]。在发展中国家，诺如病毒与死亡率高有关（约20万名5岁以下儿童）。诺如病毒是导致医院病房关闭的主要罪魁祸首，并与老年人住院和死亡率增加有关。移植患者罹患持续性诺如病毒胃肠炎的重大风险。控制和预防策略仅限于使用消毒剂和洗手液，它们的功效常常不足。因此，非常需要抗病毒治疗和预防诺如病毒感染。仅报道了少数诺如病毒复制抑制剂的事实在很大程度上可归因于阻碍无法在细胞培养物中培养人诺如病毒。带有诺沃克复制子的细胞和鼠诺如病毒感染的细胞系是评估化合物体外抗病毒活性的可用模型。人类诺如病毒已显示在小鼠，牛犊，生食性猪和黑猩猩中复制（某种程度上）。用鼠诺如病毒感染缺乏干扰素的小鼠会导致病毒引起的腹泻。在这里，我们回顾了最近的发展，以了解哪些诺如病毒蛋白或宿主细胞因子可作为抑制病毒复制的靶标。鉴于最近的进展，预计在未来几年中寻找针对诺如病毒感染的抗病毒策略的重大进展。

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