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Astrovirus Replication Is Inhibited by Nitazoxanide In Vitro and In Vivo.
Journal of Virology ( IF 4.0 ) Pub Date : 2020-02-14 , DOI: 10.1128/jvi.01706-19
Virginia Hargest 1, 2 , Bridgett Sharp 1 , Brandi Livingston 1 , Valerie Cortez 1 , Stacey Schultz-Cherry 3
Affiliation  

Astroviruses (AstV) are a leading cause of diarrhea, especially in the very young, the elderly, and immunocompromised populations. Despite their significant impact on public health, no drug therapies for astrovirus have been identified. In this study, we fill this gap in knowledge and demonstrate that the FDA-approved broad-spectrum anti-infective drug nitazoxanide (NTZ) blocks astrovirus replication in vitro with a 50% effective concentration (EC50) of approximately 1.47 μM. It can be administered up to 8 h postinfection and is effective against multiple human astrovirus serotypes, including clinical isolates. Most importantly, NTZ reduces viral shedding in vivo, exhibiting its potential as a future clinical therapeutic.IMPORTANCE Human astroviruses (HAstV) are thought to cause between 2 and 9% of acute, nonbacterial diarrhea cases in children worldwide. HAstV infection can be especially problematic in immunocompromised people and infants, where the virus has been associated with necrotizing enterocolitis and severe and persistent diarrhea, as well as rare instances of systemic and fatal disease. And yet, no antivirals have been identified to treat astrovirus infection. Our study provides the first evidence that nitazoxanide may be an effective therapeutic strategy against astrovirus disease.

中文翻译:

Nitazoxanide体外和体内抑制星状病毒复制。

星状病毒(AstV)是腹泻的主要原因,尤其是在非常年轻,老年人和免疫力低下的人群中。尽管它们对公共卫生产生重大影响,但尚未发现用于星状病毒的药物疗法。在这项研究中,我们填补了这一知识空白,并证明了FDA批准的广谱抗感染药物硝唑尼特(NTZ)在体外以约1.47μM的50%有效浓度(EC50)阻止星状病毒复制。它可以在感染后8小时内给药,对多种人类星状病毒血清型(包括临床分离株)有效。最重要的是,NTZ可以减少体内病毒的释放,具有潜在的临床应用前景。重要提示人类星状病毒(HAstV)引起2%至9%的急性 世界范围内儿童的非细菌性腹泻病例。HAstV感染在免疫力低下的人和婴儿中尤其成问题,因为该病毒与坏死性小肠结肠炎,严重和持续性腹泻以及罕见的全身性和致命性疾病有关。然而,尚未发现抗病毒药可以治疗星状病毒感染。我们的研究提供了第一个证据,表明硝唑尼特可能是抗星状病毒疾病的有效治疗策略。
更新日期:2019-11-01
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