Kumar Neeraj, Admane Nikita, Kumari Anchala, Sood Damini, Grover Sonam, Prajapati Vijay Kumar, Chandra Ramesh, Grover Abhinav
Department of Chemistry, University of Delhi, Delhi, 110007, India.
Department of Biotechnology, Jawahar Lal Nehru University, Delhi, 110067, India.
Sci Rep. 2021 Apr 7;11(1):7653. doi: 10.1038/s41598-021-86986-6.
Development of effective counteragents against the novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, requires clear insights and information for understanding the immune responses associated with it. This global pandemic has pushed the healthcare system and restricted the movement of people and succumbing of the available therapeutics utterly warrants the development of a potential vaccine to contest the deadly situation. In the present study, highly efficacious, immunodominant cytotoxic T-lymphocyte (CTL) epitopes were predicted by advanced immunoinformatics assays using the spike glycoprotein of SARS-CoV2, generating a robust and specific immune response with convincing immunological parameters (Antigenicity, TAP affinity, MHC binder) engendering an efficient viral vaccine. The molecular docking studies show strong binding of the CTL construct with MHC-1 and host membrane specific TLR2 receptors. The molecular dynamics simulation in an explicit system confirmed the stable and robust binding of CTL epitope with TLR2. Steep magnitude RMSD variation and compelling residual fluctuations existed in terminal residues and various loops of the β linker segments of TLR2-epitope (residues 105-156 and 239-254) to about 0.4 nm. The reduced R value (3.3 nm) and stagnant SASA analysis (275 nm/S/N after 8 ns and 5 ns) for protein surface and its orientation in the exposed and buried regions suggests more compactness due to the strong binding interaction of the epitope. The CTL vaccine candidate establishes a high capability to elicit the critical immune regulators, like T-cells and memory cells as proven by the in silico immunization assays and can be further corroborated through in vitro and in vivo assays.
开发针对由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)毒株引起的新型冠状病毒病(COVID-19)的有效对抗剂,需要清晰的见解和信息来理解与之相关的免疫反应。这场全球大流行给医疗系统带来了压力,限制了人们的行动,现有的治疗方法效果不佳,这完全有必要开发一种潜在疫苗来应对这种致命情况。在本研究中,使用SARS-CoV2的刺突糖蛋白,通过先进的免疫信息学分析预测了高效、免疫显性的细胞毒性T淋巴细胞(CTL)表位,产生了具有令人信服的免疫参数(抗原性、TAP亲和力、MHC结合剂)的强大而特异性的免疫反应,从而产生一种有效的病毒疫苗。分子对接研究表明CTL构建体与MHC-1和宿主膜特异性TLR2受体有强结合。在明确系统中的分子动力学模拟证实了CTL表位与TLR2的稳定而强大的结合。TLR2-表位(残基105-156和239-254)的β连接片段的末端残基和各个环中存在急剧的RMSD变化和明显的残基波动,幅度约为0.4纳米。蛋白质表面的R值降低(3.3纳米)以及在暴露和掩埋区域的停滞的溶剂可及表面积分析(8纳秒和5纳秒后为275纳米²/秒/纳)表明,由于表位的强结合相互作用,结构更加紧凑。CTL疫苗候选物具有很高的能力来引发关键的免疫调节因子,如T细胞和记忆细胞,这已通过计算机模拟免疫分析得到证实,并且可以通过体外和体内分析进一步证实。