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番茄褪绿病毒小衣壳蛋白作为筛选抗病毒药物的新靶点

Tomato Chlorosis Virus Minor Coat Protein as a Novel Target To Screen Antiviral Drugs.

作者信息

Yang Huanyu, Zu Guangcheng, Liu Yuewen, Xie Dandan, Gan Xiuhai, Song Baoan

机构信息

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi District, Guiyang 550025, China.

出版信息

J Agric Food Chem. 2020 Mar 18;68(11):3425-3433. doi: 10.1021/acs.jafc.9b08215. Epub 2020 Mar 5.

DOI:10.1021/acs.jafc.9b08215
PMID:32091891
Abstract

Minor coat protein (mCP), an important component of tomato chlorosis virus (ToCV), plays a significant role in the process of virus assembly and movement and is directly related to the virus-insect transmission. Therefore, ToCV mCP could be considered as a potent target for anti-ToCV drugs. In this study, ToCV mCP was first cloned, expressed, purified, and a novel target to screen the antiviral agents. The results showed that some antiviral compounds bound to ToCV mCP with strongly affinities in vitro, including quinazoline derivatives and , Ningnanmycin, and Ribavirin. Subsequently, three-dimensional-quantitative structure-activity relationship (3D-QSAR) analysis was performed based on the binding affinities, and the model indicated that and had indeed stronger binding effects on ToCV mCP than other quinazoline derivatives. Finally, the anti-ToCV activities of compounds and were evaluated by quantitative real-time polymerase chain reaction in vivo. Compounds and inhibited infection of ToCV in the host and as well as reduced the level of ToCV mCP gene expression. Thus, ToCV mCP can be used as a novel drug target for screening anti-ToCV agents, and the ligand-based 3D-QSAR analysis of quinazoline derivatives provided new insights into the design and optimization of novel anti-ToCV drug molecules based on ToCV mCP.

摘要

小衣壳蛋白(mCP)是番茄褪绿病毒(ToCV)的重要组成部分,在病毒组装和移动过程中发挥着重要作用,且与病毒的昆虫传播直接相关。因此,ToCV mCP可被视为抗ToCV药物的有效靶点。在本研究中,首先对ToCV mCP进行了克隆、表达、纯化,并将其作为筛选抗病毒剂的新靶点。结果表明,一些抗病毒化合物在体外与ToCV mCP具有很强的亲和力,包括喹唑啉衍生物和、宁南霉素以及利巴韦林。随后,基于结合亲和力进行了三维定量构效关系(3D-QSAR)分析,该模型表明和对ToCV mCP的结合作用确实比其他喹唑啉衍生物更强。最后,通过体内定量实时聚合酶链反应评估了化合物和的抗ToCV活性。化合物和抑制了宿主中ToCV的感染,并降低了ToCV mCP基因的表达水平。因此,ToCV mCP可作为筛选抗ToCV药物的新靶点,基于喹唑啉衍生物的配体三维定量构效关系分析为基于ToCV mCP的新型抗ToCV药物分子的设计和优化提供了新的见解。

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