Physics of virus assembly and disassembly: Energetics and dynamics

病毒组装和分解的物理学：能量学和动力学

• 批准号: 2131963
• 负责人: Roya Zandi
• 金额: $ 36.4万
• 依托单位: University of California-Riverside
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2131963&HistoricalAwards=false
• 关键词: Physics; virus; assembly; disassembly; Energetics

NONTECHNICAL SUMMARYThis award supports theoretical and computational research, and education to advance understanding of the factors contributing to the assembly and disassembly of virus particles. Viruses infect all kinds of hosts causing serious economic and health concerns worldwide. A critical step in the “life” cycle of most viruses, whether infecting bacteria, plants or animals, involves the formation of a protein shell, called the capsid that encloses the genome molecules (RNA or DNA). Viruses have not only optimized the feat of encapsulating their genetic material, but many of them have also evolved to efficiently disassemble and release their genetic materials upon entry into a host cell. Due to advances in experimental techniques at the nanoscale, the number of experiments investigating the physical basis of self-assembly and disassembly of viral particles is soaring. However, the current theoretical understanding of virus formation is incomplete. Improving this theory may guide the design of novel antiviral drugs based on direct interference of the virus assembly and/or disassembly. This award supports research aimed at making progress towards such a theory. In particular, the PI aims to develop theoretical and computational models for several new insightful experiments, which have raised basic questions relating to the formation and disassembly of virus particles. The models will describe how virus coat proteins assemble around their genetic material to form a stable shell and under what conditions a virus falls apart and release its genetic material. The results of the theoretical modeling and computer simulations will be assessed by testing model predictions against data from experiments. In advancing understanding of the formation and disassembly of viruses, this project contributes more generally to understanding the process of self-assembly which shapes much of the biomolecular world as well as biomaterials and polymer-based materials. This research on the assembly and disassembly of viruses is at the interface of condensed matter physics and biology and thus can have applications in other fields such as nanotechnology, drug delivery, and gene therapy. It can also play an important role in the development of alternative antiviral strategies based on direct interference of the capsid assembly and/or disassembly, which belong to the important areas for future studies. The research also contributes to the training of students interested in working on a new area of physical virology in a multidisciplinary field. The work of the PI will have an impact on the education of high school, undergraduate and graduate students, and in general to the training of the next generation of biological and soft condensed matter physicists.TECHNICAL SUMMARYThis award supports theoretical and computational research and education to advance understanding of the factors contributing to the assembly and disassembly of virus capsids. The current pandemic shows more than ever the urgency for learning about viruses at every level. A crucial step in the “life” cycle of most viruses, whether infecting bacteria, plants or animals, involves the formation of a protein shell, called the capsid that encloses the genome molecules (RNA or DNA). To fight viruses effectively, a comprehensive understanding of the critical steps and components of viral assembly or disassembly is essential in order to disrupt their formation. Despite a huge body of work dedicated to viruses, the knowledge about the formation of viruses and the means to combat them is still rudimentary.Several new insightful experiments have raised basic questions relating to the role of RNA in virus assembly and disassembly. The PI aims to address these questions by developing new theories and simulations. This project is aimed to address three major objectives: For objective one, the team will investigate several recent intriguing experiments corresponding to the assembly and disassembly of empty capsids built from some mutant capsid proteins. The goal of the second objective is to study the role of the genome in the kinetic pathways of virus assembly and disassembly and in defining the symmetry of viral shells with particular attention to several newly published and ongoing experiments. It appears that nucleic acid not only changes the size of the capsid but also has an impact on its symmetry. The effect of the genome on the kinetics pathways of assembly and disassembly of viral shells will also be investigated. The team will explore how it is possible for assembly or disassembly to occur spontaneously in one instance, and not in the other. Finally, disassembly also plays an important role in the formation of infectious human immunodeficiency viruses (HIV). For objective three, the team will explore how the disassembly of immature spherical HIV particles proceeds and is coupled to the formation of mature conical shells. The PI will extend the elasticity theory developed for spherical shells to explore the interactions between pentagonal defects as a spherical capsid grows, to conical and cylindrical shells. The goal is to decipher the factors that control the rate of transformation of a spherical shell to conical and cylindrical shells and find what physical considerations define the kinetics of this transformation.The fact that under many in vitro conditions single-stranded RNA viruses can spontaneously self-assemble by simply mixing their genome and capsid proteins, and by contrast, the change in pH or other thermodynamic parameters can result in the spontaneous disassembly of an otherwise stable virus, makes it possible to investigate the physical basis of virus assembly and disassembly in terms of the general principles of statistical mechanics and condensed matter physics. This project is aimed to extend modern methods of the statistical theory of soft matter such as elastic shells with topological defects, charged polymers of complex topologies, and supramolecular complexes to the emerging problems in physics of assembly and disassembly. This research on the assembly and disassembly of viruses is at the interface of condensed matter physics and biology and thus can have applications in other fields such as nanotechnology, drug delivery, and gene therapy. It can also play an important role in the development of alternative antiviral strategies based on direct interference of the capsid assembly and/or disassembly, which belong to the important areas for future studies. The research also contributes to the training of students interested in working on a new area of physical virology in a multidisciplinary field. The work of the PI will have an impact on the education of high school, undergraduate and graduate students, and in general to the training of the next generation of biological and soft condensed matter physicists.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

非技术摘要这一奖项支持理论和计算研究，以及教育，以促进对导致病毒颗粒组装和拆卸的因素的理解。病毒感染了各种宿主，引起了全球严重的经济和健康问题。大多数病毒的“生命”周期的关键步骤，无论是感染的细菌，植物还是动物，都涉及形成蛋白质壳，称为封闭基因组分子（RNA或DNA）的衣壳。病毒不仅优化了封装其遗传物质的壮举，而且其中许多也进化为有效地拆卸并释放其遗传材料进入宿主细胞。由于纳米级实验技术的进步，研究了自我组装和拆卸病毒颗粒的实验数量飙升。但是，当前对病毒形成的理论理解是不完整的。改进该理论可以基于病毒组装和/或拆卸的直接干扰来指导新型抗病毒药物的设计。该奖项支持旨在取得这种理论进步的研究。特别是，PI旨在为几个新的有见地的实验开发理论和计算模型，这些实验提出了与病毒颗粒的形成和拆卸有关的基本问题。这些模型将描述病毒涂层蛋白如何在其通用物质周围组装以形成稳定的壳，并在病毒散落并释放其遗传物质的条件下。理论建模和计算机模拟的结果将通过测试模型预测来评估实验数据的模型预测。在促进对病毒形成和拆卸的理解时，该项目更普遍地有助于理解自组装过程，从而塑造了许多生物分子世界以及生物材料和基于聚合物的材料。这项关于病毒组装和拆卸的研究是在凝结物理和生物学的界面上，因此可以在纳米技术，药物递送和基因治疗等其他领域应用。它还可以基于属于CAPSID组装和/或拆卸的直接干扰的替代抗病毒策略的发展，这属于未来研究的重要领域。这项研究还有助于培训有兴趣在多学科领域从事新的身体病毒学领域的学生。 PI的工作将对高中，本科生和研究生的教育产生影响，并且总的来说，对下一代生物学和软凝结物理学家的培训。技术摘要奖支持理论和计算研究和教育，以促进对Virus Capsids组装和解析的因素的理解。当前的大流行比以往任何时候都表现出更多关于每个级别的病毒的紧迫性。大多数病毒的“生命”周期中的关键步骤，无论是感染的细菌，植物还是动物，都涉及形成蛋白质壳，称为封闭基因组分子（RNA或DNA）的衣壳。为了有效地对抗病毒，对病毒装配或拆卸的关键步骤和组成部分的全面理解对于破坏其形成至关重要。尽管致力于病毒的大量工作，但关于病毒形成和对抗它们的手段的知识仍然是基本的。几个新的新见解实验已经提出了与RNA在病毒组装中的作用有关的基本问题。 PI旨在通过开发新的理论和模拟来解决这些问题。该项目的目的是解决三个主要目标：对于客观的目标，该团队将研究一些最近有趣的实验，这些实验与某些突变型衣壳蛋白构建的空capsids的组装和拆卸相对应。第二个目标的目的是研究基因组在病毒组装和拆卸的动力学途径中的作用，并在定义病毒壳的对称性中，特别注意几个新发表和正在进行的实验。看来核酸不仅改变了衣壳的大小，而且对其对称性产生了影响。还将研究基因组对组装和拆卸病毒壳的动力学途径的影响。该团队将探讨如何在一种情况下，而不是在另一个实例中进行赞助或拆卸。最后，拆卸在传染性人免疫缺陷病毒（HIV）的形成中也起着重要作用。对于目标三，团队将探讨未成熟球形艾滋病毒颗粒的拆卸，并与成熟的锥形壳的形成结合。 PI将扩展为球形壳开发的弹性理论，以探索五边形缺陷作为球形衣壳生长的相互作用，到圆锥形和圆柱形壳。目的是解释控制球形壳向圆锥形和圆柱形壳转化速率的因素，并找到物理上的注意事项定义了这种转化的动力学。在许多体外条件下，单链RNA病毒可以通过简单地混合其基因组和captem par的pH或captem offerers的pH或CAPSID蛋白质的变化，这一事实可以自发地组装自动组装。拆卸原本稳定的病毒，可以根据统计力学和凝结物理学的一般原理研究病毒组装的物理基础和分解。该项目旨在将软物质统计理论的现代方法扩展到诸如具有拓扑缺陷的弹性壳，复杂拓扑的带电聚合物以及超分子复合物的弹性壳，以延伸到组装物理和拆卸物理学中的新兴问题。这项关于病毒组装和拆卸的研究是在凝结物理和生物学的界面上，因此可以在纳米技术，药物递送和基因治疗等其他领域应用。它还可以基于属于CAPSID组装和/或拆卸的直接干扰的替代抗病毒策略的发展，这属于未来研究的重要领域。这项研究还有助于培训有兴趣在多学科领域从事新的身体病毒学领域的学生。 PI的工作将对高中，本科生和研究生的教育产生影响，并且总的来说，对下一代生物学和软凝结物质物理学家进行培训。该奖项反映了NSF的法定任务，并通过使用基金会的知识和更广泛的影响来审查Criteria，通过评估来诚实地通过评估来诚实地支持。

项目成果

Exact Solution for Elastic Networks on Curved Surfaces

曲面上弹性网络的精确解

• DOI: 10.1103/physrevlett.129.088001
• 发表时间: 2022
• 期刊: Physical Review Letters
• 影响因子: 8.6
• 作者: Dong, Yinan;Zandi, Roya;Travesset, Alex
• 通讯作者: Travesset, Alex