Development of a rapid antiviral screening assay based on eGFP reporter virus of Mayaro virus

Development of a rapid antiviral screening assay based on eGFP reporter virus of Mayaro virus
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DOI:
10.1016/j.antiviral.2019.05.013
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发表时间:
2019-08-01
期刊:
影响因子:
7.6
通讯作者:
Zhang, Bo
Zhang, Bo
中科院分区:
医学2区
文献类型:
--
作者:
Li, Xiaodan;Zhang, Hongqing;Zhang, Bo

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马亚罗病毒(MAYV)是一种被忽视的蚊媒甲型病毒,其引起的疾病类似于基孔肯雅病(CHIKV)、登革热(DENY)和寨卡病毒(ZIKV)。目前,还没有针对MAYV感染的特效治疗或疫苗。为了建立一种有效的MAYV抗病毒筛选方法,我们构建了MAYV熊20290株及其绿色荧光蛋白报告病毒的感染性克隆。该报告病毒在BHK-21细胞中表现出与野生型MAYV不同的高复制能力,并且在至少5轮传代中遗传稳定。EGFP的表达与病毒复制密切相关。利用已知的抑制剂利巴韦林,我们证实MAYV-EGFP报告病毒可以用于抗病毒筛选,以确定针对MAYV的特异性抑制剂。通过基于MAYV-EGFP的抗病毒实验,我们发现化合物6-氮杂环己烷具有抗CHIKV和SFV的活性,对MAYV的复制有明显的抑制作用。
Mayaro virus (MAYV) is a neglected mosquito-borne alphavirus that causes illness similar to Chikungunya (CHIKV), Dengue (DENY) and Zika virus (ZIKV). Currently, there is no specific treatment or vaccine against MAYV infection. To develop an efficient antiviral screening assay for MAYV, we constructed the infectious clones of MAYV strain BeAr 20290 and its eGFP reporter virus. The reporter virus exhibited high replication capacity indistinguishable with the wild type MAYV, and was genetically stable within at least five rounds of passages in BHK-21 cell. The expression of eGFP correlated well with the viral replication. Using the known inhibitor ribavirin, we confirmed that the MAYV-eGFP reporter virus could be used for antiviral screening to identify the specific inhibitors against MAYV. Using the MAYV-eGFP based antiviral assay, we found that the compound 6-Azauridine which had antiviral activity against CHIKV and SFV, showed a significant inhibitory effect on MAYV replication.