Khan Mohd Sultan, Shakya Madhvi, Verma Chandan Kumar
Department of Mathematics, Bioinformatics and Computer Applications, Maulana Azad National Institute of Technology, Bhopal, Madhya Pradesh 462003 India.
Virusdisease. 2024 Dec;35(4):553-566. doi: 10.1007/s13337-024-00894-7. Epub 2024 Sep 30.
The COVID-19 pandemic originated in Wuhan in 2019 due to a novel SARS-COV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) responsible for the massive number of deaths across the globe. So far, several vaccines have been developed using highly antigenic Spike protein and authorized for emergency use, reducing the severity of the infection. Nonetheless, the virus continues to evolve through multiple mutations, resulting in numerous variants with enhanced transmission that evade the vaccine-induced immune response. Given the persistently mutating nature of the SARS-COV-2 virus, peptide-based vaccines with highly conserved epitopes may offer lasting protection against evolving variants. This study presents an immunoinformatics-based identification of potentially immunogenic CD8 + T-cell epitopes (CTLs) of Spike (S), Membrane (M), Nucleocapsid (N) and Envelope (E) proteins of SARS-COV-2. By utilizing the immunoinformatic approach, 21 epitopes have successfully been evaluated, where 15, 3, 2, and 1 epitopes are respectively from Spike, Membrane, Envelope and Nucleocapsid proteins. Out of these, 20 are found to be identical with experimentally verified immunogenic epitopes, except for the novel NTQEVFAQV epitope from spike protein. These epitopes show a high degree of conservation in both former variants of concerns (VOCs), variants of interest (VOIs) and current variants under monitoring (VUMs), are non-toxic, non-homologous to humans and have a wide range of global population coverage. Furthermore, utilizing molecular docking analysis followed by molecular dynamics simulation, these epitopes have been verified as having stable interactions with their respective HLA molecules. The described framework and projected immunogenic epitopes could significantly impact the development of SARS-COV-2 vaccines based on peptides.
The online version contains supplementary material available at 10.1007/s13337-024-00894-7.
2019年新冠疫情起源于武汉，由新型严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起，该病毒在全球造成了大量死亡。到目前为止，已经研发出几种使用高抗原性刺突蛋白的疫苗并被批准用于紧急使用，降低了感染的严重程度。尽管如此，该病毒仍通过多次突变不断进化，产生了许多传播性增强的变体，这些变体能够逃避疫苗诱导的免疫反应。鉴于SARS-CoV-2病毒持续变异的特性，具有高度保守表位的基于肽的疫苗可能提供针对不断进化的变体的持久保护。本研究展示了基于免疫信息学对SARS-CoV-2刺突（S）、膜（M）、核衣壳（N）和包膜（E）蛋白潜在免疫原性CD8 + T细胞表位（CTL）的鉴定。通过利用免疫信息学方法，成功评估了21个表位，其中15个、3个、2个和1个表位分别来自刺突、膜、包膜和核衣壳蛋白。其中，除了刺突蛋白的新型NTQEVFAQV表位外，发现有20个与经实验验证的免疫原性表位相同。这些表位在前关注变体（VOC）、关注变体（VOI）和当前监测变体（VUM）中都具有高度保守性，无毒，与人类无同源性，并且具有广泛的全球人群覆盖率。此外，通过分子对接分析和分子动力学模拟，这些表位已被证实与各自的HLA分子具有稳定的相互作用。所描述的框架和预测的免疫原性表位可能会对基于肽的SARS-CoV-2疫苗的开发产生重大影响。
在线版本包含可在10.1007/s13337-024-00894-7获取的补充材料。
