PDF(Pubmed)
Abstract：
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.
摘要：
正在进行的SARS-CoV-2大流行强调了对通用和快速部署的抗病毒策略的迫切需要。虽然疫苗在控制病毒传播方面发挥了关键作用，新变种的出现继续对全球卫生构成重大挑战.这里,我们的研究重点是使用DNA适体进行抗病毒治疗的新方法，短寡核苷酸对其靶标具有高特异性和亲和力，作为SARS-CoV-2变体Omicron和JN.1的刺突蛋白的潜在抑制剂。我们的研究利用引导分子动力学（SMD）模拟来阐明专门设计的DNA适体的结合机制，AM032-4,至前述变体的受体结合结构域(RBD)。模拟揭示了对适体-RBD相互作用的详细分子见解，证明适体的潜力，以保持有效的结合面对快速的病毒进化。我们的工作不仅证明了可能的抗病毒治疗适体-RBD之间的动态相互作用，而且还引入了一种计算方法来研究适体-蛋白质相互作用。
