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.

该奖项支持理论和计算研究以及教育，以促进对有助于病毒颗粒组装和拆卸的因素的理解。病毒感染各种宿主，在世界范围内引起严重的经济和健康问题。无论是感染细菌、植物还是动物，大多数病毒“生命”周期的关键一步都涉及到一种蛋白质外壳的形成，称为衣壳，它包裹着基因组分子（RNA或DNA）。病毒不仅优化了封装其遗传物质的能力，而且许多病毒还进化到在进入宿主细胞时有效地分解和释放其遗传物质。由于纳米尺度实验技术的进步，研究病毒粒子自组装和自拆卸的物理基础的实验数量正在飙升。然而，目前对病毒形成的理论认识尚不完整。改进这一理论可以指导基于直接干扰病毒组装和/或拆卸的新型抗病毒药物的设计。该奖项支持旨在朝着这一理论取得进展的研究。特别是，PI的目标是为几个新的有见解的实验开发理论和计算模型，这些实验提出了与病毒颗粒形成和分解有关的基本问题。这些模型将描述病毒外壳蛋白如何围绕其遗传物质组装形成一个稳定的外壳，以及在什么条件下病毒分解并释放其遗传物质。理论建模和计算机模拟的结果将通过对比实验数据检验模型预测来评估。在推进对病毒形成和分解的理解的过程中，该项目有助于更广泛地理解自组装过程，该过程塑造了许多生物分子世界，以及生物材料和聚合物基材料。这项关于病毒组装和拆卸的研究是凝聚态物理和生物学的交汇点，因此可以应用于其他领域，如纳米技术、药物输送和基因治疗。它还可以在基于直接干扰衣壳组装和/或拆卸的替代抗病毒策略的开发中发挥重要作用，这属于未来研究的重要领域。该研究还有助于培养对多学科领域物理病毒学新领域工作感兴趣的学生。PI的工作将对高中，本科生和研究生的教育产生影响，并总体上对下一代生物和软凝聚态物理学家的培养产生影响。该奖项支持理论和计算研究以及教育，以促进对有助于病毒衣壳组装和拆卸的因素的理解。当前的大流行比以往任何时候都更加显示出在各个层面了解病毒的紧迫性。无论是感染细菌、植物还是动物，大多数病毒“生命”周期的一个关键步骤都涉及到一种蛋白质外壳的形成，称为衣壳，它包裹着基因组分子（RNA或DNA）。为了有效地对抗病毒，全面了解病毒组装或拆卸的关键步骤和组成部分对于破坏病毒的形成至关重要。尽管有大量的工作致力于病毒，但关于病毒的形成和对抗它们的方法的知识仍然是初级的。几个新的有见地的实验提出了有关RNA在病毒组装和拆卸中的作用的基本问题。PI旨在通过发展新的理论和模拟来解决这些问题。该项目旨在解决三个主要目标：目标一，该团队将研究最近几个有趣的实验，这些实验对应于由一些突变衣壳蛋白构建的空衣壳的组装和拆卸。第二个目标是研究基因组在病毒组装和拆卸的动力学途径中的作用，并定义病毒外壳的对称性，特别关注几个新发表的和正在进行的实验。看来核酸不仅改变衣壳的大小，而且对其对称性也有影响。基因组对病毒壳组装和拆卸动力学途径的影响也将被研究。该团队将探索如何在一个实例中自发地进行组装或拆卸，而不是在另一个实例中。最后，分解也在传染性人类免疫缺陷病毒（HIV）的形成中起着重要作用。对于目标三，该团队将探索未成熟球形HIV颗粒的分解如何进行，并与成熟锥形壳的形成相结合。PI将扩展为球形壳开发的弹性理论，以探索在球形衣壳生长时五边形缺陷之间的相互作用，到锥形和圆柱形壳。目标是破译控制球形壳向锥形和圆柱形壳转变速率的因素，并找到定义这种转变动力学的物理因素。事实上，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衣壳蛋白来自发地自我组装，相比之下，pH值或其他热力学参数的变化可以导致其他稳定病毒的自发分解，这使得根据统计力学和凝聚态物理的一般原理来研究病毒组装和拆卸的物理基础成为可能。本项目旨在扩展软物质统计理论的现代方法，如具有拓扑缺陷的弹性壳，复杂拓扑的带电聚合物和超分子复合物，以解决新出现的组装和拆卸物理问题。这项关于病毒组装和拆卸的研究是凝聚态物理和生物学的交汇点，因此可以应用于其他领域，如纳米技术、药物输送和基因治疗。它还可以在基于直接干扰衣壳组装和/或拆卸的替代抗病毒策略的开发中发挥重要作用，这属于未来研究的重要领域。该研究还有助于培养对多学科领域物理病毒学新领域工作感兴趣的学生。PI的工作将对高中，本科生和研究生的教育产生影响，并总体上对下一代生物和软凝聚态物理学家的培养产生影响。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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