自从严重急性呼吸系统综合症冠状病毒2(SARS-CoV-2)爆发以来,已经提出了几种解决方案来管理这种疾病。控制这种病毒的最可行选择是生产有效的疫苗。目前大多数SARS-CoV-2疫苗都集中在输注尖峰蛋白上。刺突作为三聚体存在,通过其受体结合域(RBD)与血管紧张素转换酶2(ACE2)受体结合,在感染宿主细胞中起着至关重要的作用。铁蛋白蛋白,一种天然存在的铁储存蛋白,由于其自组装特性,已经引起了疫苗生产的关注,无毒性质,和生物相容性。铁蛋白纳米笼最近已用于开发SARS-CoV-2疫苗接种,不仅引起长期保护性记忆细胞,而且引起持续的抗体应答。在这项研究中,计算机模拟研究的组合,包括分子对接,分子动力学模拟,并进行了免疫模拟,以计算模拟铁蛋白纳米笼上的单体刺突蛋白,并首次评估其稳定性和相互作用。建模复合体的结构动力学表现出明显的稳定性。特别是,单体刺突-铁蛋白复合物内的受体结合结构域(RBD)和铁蛋白显示出显著的稳定性。二级结构缺乏改变进一步支持了复合物的整体稳定性。铁蛋白和尖峰之间距离的下降表明随着时间的推移存在强烈的相互作用。互相关矩阵显示,单体刺突和铁蛋白彼此相向移动,支持刺突和铁蛋白之间的稳定相互作用。Further,铁蛋白单元内单体刺突蛋白的方向促进了关键表位的暴露,特异性向上活性受体结合域(RBD),使与ACE2受体的有效相互作用。该模型的免疫模拟表明,对人体的细胞和体液免疫都有高水平的刺激。还发现,无论不同变体中的突变尖峰如何,所采用的模型都是有效的。这些发现揭示了SARS-CoV-2-铁蛋白纳米颗粒疫苗的现状,并可用作其他类似疫苗设计的框架。
Since the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak, several solutions have been proposed to manage the disease. The most viable option for controlling this virus is to produce effective vaccines. Most of the current SARS-CoV-2 vaccines have focused on the infusion spike protein. Spike exists as a trimer and plays a vital role in infecting host cells by binding to the Angiotensin-Converting Enzyme 2 (ACE2) receptor through its Receptor Binding Domain (RBD).
Ferritin protein, a naturally occurring iron-storage protein, has gained attention for vaccine production due to its self-assembling property, non-toxic nature, and biocompatibility.
Ferritin nanocages have recently been employed in the development of a SARS-CoV-2 vaccination eliciting not only long-term protective memory cells but also a sustained antibody response. In this study, a combination of in silico investigations including molecular docking, molecular dynamics simulations, and immune simulations were carried out to computationally model the monomeric spike protein on the ferritin nanocage as well as to evaluate its stability and interactions for the first time. The structural dynamics of the modeled complex demonstrated noticeable stability. In particular, the Receptor Binding Domain (RBD) and
ferritin within the monomeric spike-
ferritin complex illustrated significant stability. The lack of alterations in the secondary structure further supported the overall steadiness of the complex. The decline in the distance between
ferritin and spike suggests a strong interaction over time. The cross-correlation matrices revealed that the monomeric spike and ferritin move towards each other supporting the stable interaction between spike and
ferritin. Further, the orientation of monomeric spike protein within the ferritin unit facilitated the exposure of critical epitopes, specifically upward active Receptor Binding Domain (RBD), enabling effective interactions with the ACE2 receptor. The immune simulations of the model indicated high-level stimulations of both cellular and humoral immunity in the human body. It was also found that the employed model is effective regardless of the mutated spikes in different variants. These findings shed light on the current status of the SARS-CoV-2-ferritin nanoparticle vaccines and could be used as a framework for other similar vaccine designs.