Raguram Aditya, Sasisekharan V, Sasisekharan Ram
Harvard College, Harvard University, Cambridge, MA 02138, USA.
Department of Biological Engineering, Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Trends Microbiol. 2017 Jun;25(6):438-446. doi: 10.1016/j.tim.2016.12.007. Epub 2017 Jan 13.
Recent developments of rational strategies for the design of antiviral therapies, including monoclonal antibodies (mAbs), have naturally relied extensively on available viral structural information. As new strategies continue to be developed, it is equally important to continue to refine our understanding and interpretation of viral structural data. There are known limitations to the traditional (Caspar-Klug) theory for describing virus capsid structures that involves subdividing a capsid into triangular subunits. In this context, we describe a more general polyhedral framework for describing virus capsid structures that is able to account for many of these limitations, including a more thorough characterization of intersubunit interfaces. Additionally, our use of pentagonal subunits instead of triangular ones accounts for the intrinsic chirality observed in all capsids. In conjunction with the existing theory, the framework presented here provides a more complete picture of a capsid's structure and therefore can help contribute to the development of more effective antiviral strategies.
包括单克隆抗体(mAb)在内的抗病毒疗法合理设计策略的最新进展,自然在很大程度上依赖于现有的病毒结构信息。随着新策略不断被开发,持续完善我们对病毒结构数据的理解和解读同样重要。传统的(卡斯帕 - 克卢格)描述病毒衣壳结构的理论存在已知局限性,该理论将衣壳细分为三角形亚基。在此背景下,我们描述了一个更通用的多面体框架来描述病毒衣壳结构,它能够解释许多这些局限性,包括对亚基间界面更全面的表征。此外,我们使用五边形亚基而非三角形亚基,解释了在所有衣壳中观察到的内在手性。结合现有理论,这里提出的框架提供了更完整的衣壳结构图景,因此有助于推动更有效的抗病毒策略的发展。