Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun 130012, China.
Int J Mol Sci. 2023 Sep 23;24(19):14471. doi: 10.3390/ijms241914471.
The disease of SARS-CoV-2 has caused considerable morbidity and mortality globally. Spike proteins on the surface of SARS-CoV-2 allow it to bind with human cells, leading to infection. Fullerenes and their derivatives are promising SARS-CoV-2 inhibitors and drug-delivery vehicles. In this study, Gaussian accelerated molecular dynamics simulations and the Markov state model were employed to delve into the inhibitory mechanism of Fullerene-linear-polyglycerol-b-amine sulfate (F-LGPS) on spike proteins. During the study, it was discovered that fullerene derivatives can operate at the interface of the receptor-binding domain (RBD) and the N-terminal domain (NTD), keeping structural domains in a downward conformation. It was also observed that F-LGPS demonstrated superior inhibitory effects on the XBB variant in comparison to the wild-type variant. This study yielded invaluable insights for the potential development of efficient therapeutics targeting the spike protein of SARS-CoV-2.
SARS-CoV-2 疾病在全球范围内造成了相当高的发病率和死亡率。SARS-CoV-2 表面的刺突蛋白使其能够与人体细胞结合，导致感染。富勒烯及其衍生物是很有前途的 SARS-CoV-2 抑制剂和药物输送载体。在这项研究中，使用高斯加速分子动力学模拟和马尔可夫状态模型深入研究了富勒烯-线性-聚甘油-b-胺硫酸盐（F-LGPS）对刺突蛋白的抑制机制。研究过程中发现，富勒烯衍生物可以在受体结合域（RBD）和 N 端结构域（NTD）的界面上发挥作用，使结构域保持向下构象。还观察到 F-LGPS 对 XBB 变体的抑制作用优于野生型变体。这项研究为针对 SARS-CoV-2 刺突蛋白的高效治疗药物的潜在开发提供了宝贵的见解。
