Williamson David J, Zaza Cecilia, Carlon-Andres Irene, Starling Tobias, Gentili Alessia, Thrush Joseph W, Le Bas Audrey, Ravi Ravi Teja, Neil Stuart, Owens Ray J, Dumoux Maud, Simoncelli Sabrina, Padilla-Parra Sergi
Department of Infectious Diseases, King's College London, Faculty of Life Sciences & Medicine, London, U.K.
London Centre for Nanotechnology, University College London, London, U.K.
Biochem Soc Trans. 2025 Jun 30;53(3):643-652. doi: 10.1042/BST20240769.
Understanding how viruses enter and fuse with host cells is crucial for developing effective antiviral therapies. The process of viral entry and fusion involves a series of complex steps that allow the virus to breach the host cell membrane and deliver its genetic material inside, with viral fusogens often co-operating to attain the required energy for successful membrane fusion. This co-operative clustering of fusogens in viral envelopes is similar to receptor clustering in cellular systems, where receptors aggregate to initiate signalling cascades. Single-molecule localisation microscopy (SMLM) approaches have emerged as powerful tools to study these intricate mechanisms, allowing the observation of proteins with unprecedented levels of detail. These technologies provide unparalleled insights into the dynamics of viral entry and fusion at a molecular level, revealing how the co-ordinated action of fusogens facilitates membrane fusion. By employing the newest advances in SMLM techniques, such as DNA-PAINT and MINFLUX, we anticipate that precise information on the key steps of viral fusion can be revealed with high spatial and temporal resolutions, identifying critical points in the process that can be targeted by antiviral strategies.
了解病毒如何进入宿主细胞并与之融合对于开发有效的抗病毒疗法至关重要。病毒进入和融合的过程涉及一系列复杂步骤,使病毒能够突破宿主细胞膜并将其遗传物质传递到细胞内,病毒融合蛋白通常协同作用以获得成功膜融合所需的能量。病毒包膜中融合蛋白的这种协同聚集类似于细胞系统中的受体聚集,在细胞系统中受体会聚集以启动信号级联反应。单分子定位显微镜(SMLM)方法已成为研究这些复杂机制的强大工具,能够以前所未有的细节水平观察蛋白质。这些技术在分子水平上为病毒进入和融合的动力学提供了无与伦比的见解,揭示了融合蛋白的协同作用如何促进膜融合。通过采用SMLM技术的最新进展,如DNA-PAINT和MINFLUX,我们预计可以以高空间和时间分辨率揭示病毒融合关键步骤的精确信息,确定该过程中可作为抗病毒策略靶点的关键点。
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