以RNA聚合酶为靶点的抗槟榔黄化病毒药物虚拟筛选  

Virtual screening of anti-areca palm velarivirus 1 drugs tageted at RNA polymerase

作　　者：曾涛 吉训聪[1] 芮凯[1] 符美英[1] 田威 马瑞 黄伟康 ZENG Tao;JI Xun-cong;RUI Kai;FU Mei-ying;TIAN Wei;MA Rui;HUANG Wei-kang(Hainan Academy of Agricultural Sciences,Institute of Plant Protection,Scientific Observation and Experiment Station of Crop Pests in HaiKou,Ministry of Agriculture and Rural Affairs,Key Laboratory of Plant Disease and Pest Control of Hainan Province,Haikou 571100,China)

机构地区：[1]海南省农业科学院植物保护研究所农业农村部海口作物有害生物科学观测实验站海南省植物病虫害防控重点实验室,海口571100

出　　处：《农药》2022年第1期24-28,33,共6页Agrochemicals

基　　金：海南省重大科技计划项目(zdkj201817)。

摘　　要：[目的]基于槟榔黄化病毒的RNA依赖性RNA聚合酶筛选抗槟榔黄化病毒先导化合物。[方法]使用基于片段的药物设计方法,从PADFrag农药分子片段子库中筛选出14个片段作为骨架进行生长,得到140个分子,取11个CDOCKER得分靠前的分子进行分子动力学模拟和MM/GBSA计算以评估这些分子与RNA依赖性RNA聚合酶的亲和力,最后确定2个优选分子作为潜在的抗槟榔黄化病毒先导化合物。[结果]2个优选分子能以范德华力、静电相互作用以及氢键等方式与靶点稳固结合,有潜在的抗槟榔黄化病毒活性。[结论]2个优选分子可作为先导化合物用于新型抗槟榔黄化病毒药物开发。[Aims] This study aims to screen out lead compounds against areca palm velarivirus 1 based on RNA-Dependent RNA Polymerase target. [Methods] Through the fragment-based drug design, 14 fragments were selected from the PADFrag pesticide fragment sub-library as the scaffolds for growth, and 140 molecules were obtained. Then the 11 molecules with the highest CDOCKER score were selected for molecular dynamics simulation and MM/GBSA calculation to evaluate their affinity to RNA-dependent RNA polymerase, and finally two molecules were identified as potential lead compounds against areca palm velarivirus 1. [Results] The two selected molecules could bind firmly to the target through van der Waals force, electrostatic interaction and hydrogen bonding, which indicated that they have potential activity against areca palm velarivirus 1. [Conclusions] The two preferred molecules could be used as lead compounds in the development of new anti-areca palm velarivirus 1 drugs.

关 键 词：抗槟榔黄化病毒药物 RNA聚合酶 虚拟筛选 分子动力学模拟 MM/GBSA计算 药物设计 

分 类 号：S482.2[农业科学—农药学]