Cap-snatching inhibitors of influenza virus are inhibitory to the in vitro transcription of rice stripe virus

Cap-snatching inhibitors of influenza virus are inhibitory to the in vitro transcription of rice stripe virus
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流感病毒抢帽抑制剂抑制水稻条纹病毒体外转录

DOI:
10.1186/s42483-022-00141-1
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发表时间:
2022-09-26
影响因子:
3.4
通讯作者:
Du, Zhenguo
Du, Zhenguo
中科院分区:
农林科学2区
文献类型:
--
作者:
Lin, Wenzhong;Zha, Qingchen;Du, Zhenguo

文献摘要

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水稻条纹病毒(Rice Stripe Virus,RSV)是东亚地区重要的水稻病毒病原之一。RSV的转录由夺帽启动,这是流感病毒(IFV)共有的机制。这提供了靶向IFV的夺帽的抗病毒化合物(其中许多已经商购获得)可以抑制RSV转录的可能性。然而,到目前为止,还没有一种方便而廉价的系统可以让研究人员测试这一想法。在这里,我们表明,纯化的呼吸道合胞病毒在体外进行转录和转录很容易检测巢式逆转录-聚合酶链反应(RT-PCR)。使用该系统,我们测试了2,4-二氧代-4-苯基丁酸(DPBA)和pimodivir(两种众所周知的IFV夺帽抑制剂)以及利巴韦林(一种广谱抗病毒化合物,其靶标仍然难以捉摸)的作用。在含有2.5 ng/μ L纯化RSV的反应混合物中,DPBA和pimodivir分别在10和100 μ M浓度下消除RSV转录。相反,从利巴韦林中没有检测到抑制作用,甚至在高达400 μ M的浓度下。这些结果表明,IFV的至少一些夺帽抑制剂抑制RSV转录。这些化合物,这可以确定与实验系统在这里描述,可以作为开发抗RSV或相关植物病毒的抗病毒药物的起点。
Rice stripe virus (RSV) is one of the most important viral pathogens of rice in East Asia. The transcription of RSV is initiated by cap-snatching, a mechanism shared by influenza virus (IFV). This lends the possibility that antiviral compounds targeting the cap-snatching of IFV, many of which have been commercially available, may inhibit RSV transcription. A convenient and inexpensive system allowing researchers to test this idea, however, has been unavailable to date. Here, we show that purified RSV performs transcription in vitro and the transcription was readily detectable by nested reverse transcription-polymerase chain reaction (RT-PCR). With this system, we tested the effects of 2,4-dioxo-4-phenylbutanoic acid (DPBA) and pimodivir, two well-known IFV cap-snatching inhibitors, as well as ribavirin, a broad-spectrum antiviral compound whose targets remain elusive. In reaction mixtures containing 2.5 ng/mu L of purified RSV, DPBA and pimodivir abolished RSV transcription at a concentration of 10 and 100 mu M, respectively. In contrast, no inhibitory effect was detected from ribavirin, even at a concentration as high as 400 mu M. These results suggest that at least some cap-snatching inhibitors of IFV are inhibitory to RSV transcription. These compounds, which can be identified with the experimental system described here, may serve as starting points in developing antivirals against RSV or related plant viruses.