The objective of this critical review is to provide an overview of how emerging bioanalytical techniques are expanding our understanding of the complex physicochemical nature of virus interactions with host cell surfaces. Herein, selected model viruses representing both non-enveloped (simian virus 40 and human norovirus) and enveloped (influenza A virus, human herpes simplex virus, and human immunodeficiency virus type 1) viruses are highlighted. The technologies covered utilize a wide range of cell membrane mimics, from supported lipid bilayers (SLBs) containing a single purified host membrane component to SLBs derived from the plasma membrane of a target cell, which can be compared with live-cell experiments to better understand the role of individual interaction pairs in virus attachment and entry. These platforms are used to quantify binding strengths, residence times, diffusion characteristics, and binding kinetics down to the single virus particle and single receptor, and even to provide assessments of multivalent interactions. The technologies covered herein are surface plasmon resonance (SPR), quartz crystal microbalance with dissipation (QCM-D), dynamic force spectroscopy (DFS), total internal reflection fluorescence (TIRF) microscopy combined with equilibrium fluctuation analysis (EFA) and single particle tracking (SPT), and finally confocal microscopy using multi-labeling techniques to visualize entry of individual virus particles in live cells. Considering the growing scientific and societal needs for untangling, and interfering with, the complex mechanisms of virus binding and entry, we hope that this review will stimulate the community to implement these emerging tools and strategies in conjunction with more traditional methods. The gained knowledge will not only contribute to a better understanding of the virus biology, but may also facilitate the design of effective inhibitors to block virus entry.

这篇批判性评论的目的是概述新兴的生物分析技术如何扩大我们对病毒与宿主细胞表面相互作用的复杂物理化学性质的理解。在此，突出显示了代表非包膜病毒（猿猴病毒 40 和人类诺如病毒）和包膜病毒（甲型流感病毒、人类单纯疱疹病毒和人类免疫缺陷病毒 1 型）的选定模型病毒。涵盖的技术利用了广泛的细胞膜模拟物，从含有单一纯化宿主膜成分的支持脂质双层 (SLB) 到源自靶细胞质膜的 SLB，可以将其与活细胞实验进行比较以更好地理解个体相互作用对在病毒附着和进入中的作用。这些平台用于量化结合强度、停留时间、扩散特性和结合动力学到单个病毒颗粒和单个受体，甚至提供多价相互作用的评估。本文涵盖的技术包括表面等离子共振 (SPR)、带耗散的石英晶体微天平 (QCM-D)、动态力光谱 (DFS)、全内反射荧光 (TIRF) 显微镜结合平衡波动分析 (EFA) 和单粒子跟踪(SPT)，最后是使用多标记技术的共聚焦显微镜，以可视化单个病毒颗粒在活细胞中的进入。考虑到科学和社会对解开和干扰病毒结合和进入的复杂机制日益增长的需求，我们希望这次审查将激励社区结合更传统的方法来实施这些新兴工具和策略。所获得的知识不仅有助于更好地了解病毒生物学，还可能有助于设计有效的抑制剂来阻止病毒进入。