Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South Africa.
Research Unit in Bioinformatics (RUBi), Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South Africa.
Viruses. 2020 Mar 31;12(4):387. doi: 10.3390/v12040387.
The assembly of picornavirus capsids proceeds through the stepwise oligomerization of capsid protein subunits and depends on interactions between critical residues known as hotspots. Few studies have described the identification of hotspot residues at the protein subunit interfaces of the picornavirus capsid, some of which could represent novel drug targets. Using a combination of accessible web servers for hotspot prediction, we performed a comprehensive bioinformatic analysis of the hotspot residues at the intraprotomer, interprotomer and interpentamer interfaces of the Theiler's murine encephalomyelitis virus (TMEV) capsid. Significantly, many of the predicted hotspot residues were found to be conserved in representative viruses from different genera, suggesting that the molecular determinants of capsid assembly are conserved across the family. The analysis presented here can be applied to any icosahedral structure and provides a platform for in vitro mutagenesis studies to further investigate the significance of these hotspots in critical stages of the virus life cycle with a view to identify potential targets for antiviral drug design.
小核糖核酸病毒衣壳的组装是通过衣壳蛋白亚基的逐步寡聚化进行的，并且依赖于称为热点的关键残基之间的相互作用。很少有研究描述了小核糖核酸病毒衣壳蛋白亚基界面上热点残基的鉴定，其中一些可能代表新的药物靶点。本研究使用可访问的热点预测网络服务器的组合，对 Theiler's 鼠脑脊髓炎病毒 (TMEV) 衣壳的单体内部、单体之间和五聚体之间界面的热点残基进行了全面的生物信息学分析。重要的是，许多预测的热点残基在来自不同属的代表性病毒中被发现是保守的，这表明衣壳组装的分子决定因素在整个家族中是保守的。这里提出的分析可以应用于任何二十面体结构，并为体外诱变研究提供了一个平台，以进一步研究这些热点在病毒生命周期的关键阶段的意义，以期确定抗病毒药物设计的潜在靶标。
