Department of Chemistry and Biochemistry, University of Texas at El Paso, El Paso, Texas 79968, United States.
J Phys Chem B. 2021 Dec 9;125(48):13122-13131. doi: 10.1021/acs.jpcb.1c07436. Epub 2021 Nov 30.
Solid core nanoparticles (NPs) coated with sulfonated ligands that mimic heparan sulfate proteoglycans (HSPGs) can exhibit virucidal activity against many viruses that utilize HSPG interactions with host cells for the initial stages of infection. How the interactions of these NPs with large capsid segments of HSPG-interacting viruses lead to their virucidal activity has been unclear. Here, we describe the interactions between sulfonated NPs and segments of the human papilloma virus type 16 (HPV16) capsids using atomistic molecular dynamics simulations. The simulations demonstrate that the NPs primarily bind at the interfaces of two HPV16 capsid proteins. After equilibration, the distances and angles between capsid proteins in the capsid segments are larger for the systems in which the NPs bind at the interfaces of capsid proteins. Over time, NP binding can lead to breaking of contacts between two neighboring proteins. The revealed mechanism of NPs targeting the interfaces between pairs of capsid proteins can be utilized for designing new generations of virucidal materials and contribute to the development of new broad-spectrum non-toxic virucidal materials.
固核纳米粒子（NPs）表面覆盖有模拟硫酸乙酰肝素蛋白聚糖（HSPG）的磺酸配体，对许多利用 HSPG 与宿主细胞相互作用进行初始感染阶段的病毒具有病毒杀灭活性。这些 NPs 与 HSPG 相互作用的病毒的大衣壳片段相互作用如何导致其病毒杀灭活性尚不清楚。在这里，我们使用原子分子动力学模拟描述了磺化 NPs 与人类乳头瘤病毒 16 型（HPV16）衣壳片段之间的相互作用。模拟表明， NPs 主要结合在 HPV16 衣壳蛋白的界面上。平衡后，在 NPs 结合在衣壳蛋白界面的系统中，衣壳片段中衣壳蛋白之间的距离和角度更大。随着时间的推移，NP 结合可能导致两个相邻蛋白之间的接触破裂。所揭示的 NPs 靶向衣壳蛋白对之间界面的机制可用于设计新一代的病毒杀灭材料，并有助于开发新的广谱无毒病毒杀灭材料。
