The COVID-19 pandemic, which was caused by SARS-CoV-2, initiated a global health crisis in 2019. SARS-CoV-2 is a single-stranded RNA virus encased in a lipid envelope that houses key structural proteins, including the Spike glycoprotein, which mediates viral entry into host cells. Within the Spike protein, the S2 subunit, and particularly its fusion domain, plays a critical role in merging viral and host membranes. Understanding the fusion domain interactions at the molecular level is important for advancing applications such as the development of novel antiviral therapies. This study investigates the self-assembly of SARS-CoV-2 S2 subunit fusion peptides (FPs) and their interaction with biomimetic plasma membrane (PM) models composed of physiological mixes of phospholipids, sphingomyelin, and cholesterol. Complementary techniques, including atomic force microscopy, neutron reflectometry and grazing incidence X-ray diffraction, provided detailed insights into lipid nano-mechanics and in-plane molecular structure. Our findings reveal several types of FP assemblies at the PM interface, including the formation of rigid fibres, spiral structures, and segregated domains. These behaviours are influenced by FP intrinsic features such as hydrophobicity and molecular structure, and the resultant interactions with lipid headgroups and tail regions. This work enhances our molecular-level understanding of FP-lipid interactions, shedding light on viral entry mechanisms. Furthermore, the ability of these peptides to self-assemble, modulated by the surrounding lipid environment, positions them as promising building blocks for innovative functional biomaterials.

中文翻译：

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深入了解 SARS-CoV-2 融合肽与仿生质膜模型的自组装和相互作用


由 SARS-CoV-2 引起的 COVID-19 大流行在 2019 年引发了一场全球健康危机。SARS-CoV-2 是一种包裹在脂质包膜中的单链 RNA 病毒，该包膜包含关键结构蛋白，包括介导病毒进入宿主细胞的刺突糖蛋白。在 Spike 蛋白中，S2 亚基，尤其是其融合结构域，在合并病毒膜和宿主膜中起着关键作用。了解分子水平上的融合结构域相互作用对于推进新型抗病毒疗法开发等应用非常重要。本研究研究了 SARS-CoV-2 S2 亚基融合肽 （FP） 的自组装及其与由磷脂、鞘磷脂和胆固醇的生理混合物组成的仿生质膜 （PM） 模型的相互作用。互补技术，包括原子力显微镜、中子反射法和掠入射 X 射线衍射，为脂质纳米力学和面内分子结构提供了详细的见解。我们的研究结果揭示了 PM 界面处的几种类型的 FP 组装体，包括刚性纤维的形成、螺旋结构和分离域。这些行为受 FP 固有特征（如疏水性和分子结构）以及与脂质头部基团和尾部区域的相互作用的影响。这项工作增强了我们对 FP-脂质相互作用的分子水平理解，阐明了病毒进入机制。此外，这些肽在周围脂质环境的调节下进行自我组装的能力使它们成为创新功能性生物材料的有前途的构建块。