番茄斑萎病毒蛋白结构及其抑制剂作用机制研究进展

Progress on the protein structure of tomato spotted wilt virus and the mechanism of inhibitor action

番茄斑萎病毒(tomato spotted wilt virus,TSWV)基因组可编码RdRp、NSm、NSs、Gc、Gn和N等多种蛋白,目前,相关研究主要集中在植物(番茄和辣椒)对TSWV的抗病基因(Sw-5b和Tsw)所介导的抗性以及药剂对TSWV N蛋白的抑制作用。TSWV蛋白具有作为药剂分子靶标的潜力,但关于TSWV蛋白与药剂的作用机制尚未见系统、全面的研究报道。本文从结构生物学的角度出发,详细介绍了目前已经被解析的TSWV病毒蛋白三维结构,并通过AlphaFold2模型预测了尚未被解析的4种TSWV蛋白结构;同时,综述了TSWV抗性基因和TSWV抑制剂在植物保护领域的研究应用进展。以宁南霉素、盐酸吗啉胍和利巴韦林等药剂为例,分析其可能作用于TSWV蛋白的分子机理,并预测了这些药剂与TSWV蛋白可能的作用位点,旨在为后续深入挖掘和探索新型抗TSWV药剂提供理论依据。

The genome of tomato spotted wilt virus(TSWV)can encode various proteins,including RdRp,NSm,NSs,Gc,Gn,and N.Existing research primarily focuses on plant(tomato and chili pepper)resistance to TSWV mediated by resistance genes(Sw-5b and Tsw).Furthermore,the inhibitory effects of agents on the TSWV N proteins have been investigated.TSWV proteins have the potential to be used as molecular targets for pharmaceutical agents,however,the mechanism of action between TSWV proteins and pharmaceutical agents has not been systematically and comprehensively reported.This study presents a detailed analysis of the three-dimensional structures of resolved TSWV proteins and predicts the structures of four unresolved TSWV proteins using AlphaFold2 modeling.It also summarizes the advancement and application of TSWV resistance genes and TSWV inhibitors in plant protection.The potential molecular mechanisms of ningnanmycin,moroxydine,and ribavirin on TSWV proteins were analyzed,along with their possible sites of action.The aim is to establish a theoretical foundation for subsequent comprehensive excavation and exploration of novel agents with anti-TSWV properties.