Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing 210093, China.
State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing 210093, China.
Molecules. 2024 May 9;29(10):2215. doi: 10.3390/molecules29102215.
The ongoing SARS-CoV-2 pandemic has underscored the urgent need for versatile and rapidly deployable antiviral strategies. While vaccines have been pivotal in controlling the spread of the virus, the emergence of new variants continues to pose significant challenges to global health. Here, our study focuses on a novel approach to antiviral therapy using DNA aptamers, short oligonucleotides with high specificity and affinity for their targets, as potential inhibitors against the spike protein of SARS-CoV-2 variants Omicron and JN.1. Our research utilizes steered molecular dynamics (SMD) simulations to elucidate the binding mechanisms of a specifically designed DNA aptamer, AM032-4, to the receptor-binding domain (RBD) of the aforementioned variants. The simulations reveal detailed molecular insights into the aptamer-RBD interaction, demonstrating the aptamer's potential to maintain effective binding in the face of rapid viral evolution. Our work not only demonstrates the dynamic interaction between aptamer-RBD for possible antiviral therapy but also introduces a computational method to study aptamer-protein interactions.
持续的 SARS-CoV-2 大流行凸显了迫切需要多功能且可快速部署的抗病毒策略。虽然疫苗在控制病毒传播方面发挥了关键作用，但新变体的出现继续对全球健康构成重大挑战。在这里，我们的研究侧重于使用 DNA 适体作为抗病毒治疗的新方法，DNA 适体是一种具有高度特异性和亲和力的短寡核苷酸，可作为针对 SARS-CoV-2 变体奥密克戎和 JN.1 的刺突蛋白的潜在抑制剂。我们的研究利用导向分子动力学（SMD）模拟来阐明专门设计的 DNA 适体 AM032-4 与上述变体的受体结合域（RBD）的结合机制。模拟揭示了适体-RBD 相互作用的详细分子见解，表明适体在面对快速病毒进化时保持有效结合的潜力。我们的工作不仅展示了适体-RBD 之间可能的抗病毒治疗的动态相互作用，还介绍了一种用于研究适体-蛋白质相互作用的计算方法。
