Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
J Virol. 2020 Feb 14;94(5). doi: 10.1128/JVI.01706-19.
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 with a 50% effective concentration (EC) 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 , exhibiting its potential as a future clinical therapeutic. 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.
星状病毒(AstV)是导致腹泻的主要原因之一,尤其是在婴幼儿、老年人和免疫功能低下的人群中。尽管它们对公共卫生有重大影响,但尚未发现针对星状病毒的药物治疗方法。在这项研究中,我们填补了这一知识空白,并证明了美国食品和药物管理局(FDA)批准的广谱抗感染药物硝唑尼特(NTZ)可通过大约 1.47μM 的 50%有效浓度(EC)阻断星状病毒复制。它可以在感染后 8 小时内给药,并且对多种人类星状病毒血清型有效,包括临床分离株。最重要的是,NTZ 可减少病毒脱落,显示出其作为未来临床治疗药物的潜力。据认为,人类星状病毒(HAstV)在全球范围内导致 2%至 9%的急性非细菌性腹泻病例。在免疫功能低下的人群和婴儿中,星状病毒感染可能特别成问题,因为该病毒与坏死性小肠结肠炎以及严重和持续的腹泻以及罕见的全身和致命疾病有关。然而,尚未发现用于治疗星状病毒感染的抗病毒药物。我们的研究首次提供了硝唑尼特可能是针对星状病毒疾病的有效治疗策略的证据。