Awad Nourelislam, Mohamed Rania Hassan, Ghoneim Nehal I, Elmehrath Ahmed O, El-Badri Nagwa
Center of Excellence for Stem Cells and Regenerative Medicine (CESC), Zewail City of Science and Technology, Giza, Egypt.
Center of Informatics Sciences, Nile University, Giza, Egypt.
J Genet Eng Biotechnol. 2022 Apr 20;20(1):60. doi: 10.1186/s43141-022-00344-1.
The novel coronavirus (SARS-CoV-2) caused lethal infections worldwide during an unprecedented pandemic. Identification of the candidate viral epitopes is the first step in the design of vaccines against the viral infection. Several immunoinformatic approaches were employed to identify the SARS-CoV-2 epitopes that bind specifically with the major histocompatibility molecules class I (MHC-I). We utilized immunoinformatic tools to analyze the whole viral protein sequences, to identify the SARS-CoV-2 epitopes responsible for binding to the most frequent human leukocyte antigen (HLA) alleles in the Egyptian population. These alleles were also found with high frequency in other populations worldwide.
Molecular docking approach showed that using the co-crystallized MHC-I and T cell receptor (TCR) instead of using MHC-I structure only, significantly enhanced docking scores and stabilized the conformation, as well as the binding affinity of the identified SARS-CoV-2 epitopes. Our approach directly predicts 7 potential vaccine subunits from the available SARS-CoV-2 spike and ORF1ab protein sequence. This prediction has been confirmed by published experimentally validated and in silico predicted spike epitope. On the other hand, we predicted novel epitopes (RDLPQGFSA and FCLEASFNY) showing high docking scores and antigenicity response with both MHC-I and TCR. Moreover, antigenicity, allergenicity, toxicity, and physicochemical properties of the predicted SARS-CoV-2 epitopes were evaluated via state-of-the-art bioinformatic approaches, showing high efficacy of the proposed epitopes as a vaccine candidate.
Our predicted SARS-CoV-2 epitopes can facilitate vaccine development to enhance the immunogenicity against SARS-CoV-2 and provide supportive data for further experimental validation. Our proposed molecular docking approach of exploiting both MHC and TCR structures can be used to identify potential epitopes for most microbial pathogens, provided the crystal structure of MHC co-crystallized with TCR.
新型冠状病毒（SARS-CoV-2）在一场史无前例的大流行期间在全球引发了致命感染。鉴定候选病毒表位是设计针对病毒感染疫苗的第一步。采用了多种免疫信息学方法来鉴定与主要组织相容性复合体I类（MHC-I）特异性结合的SARS-CoV-2表位。我们利用免疫信息学工具分析整个病毒蛋白序列，以鉴定负责与埃及人群中最常见的人类白细胞抗原（HLA）等位基因结合的SARS-CoV-2表位。这些等位基因在世界其他人群中也有较高频率出现。
分子对接方法表明，使用共结晶的MHC-I和T细胞受体（TCR）而非仅使用MHC-I结构，显著提高了对接分数，稳定了构象以及所鉴定的SARS-CoV-2表位的结合亲和力。我们的方法直接从可用的SARS-CoV-2刺突蛋白和ORF1ab蛋白序列中预测出7个潜在的疫苗亚基。这一预测已通过已发表的经实验验证和计算机模拟预测的刺突表位得到证实。另一方面，我们预测了新的表位（RDLPQGFSA和FCLEASFNY），它们与MHC-I和TCR均显示出高对接分数和抗原性反应。此外，通过先进的生物信息学方法评估了预测的SARS-CoV-2表位的抗原性、致敏性、毒性和理化性质，表明所提出的表位作为疫苗候选物具有高效性。
我们预测的SARS-CoV-2表位可促进疫苗开发，以增强针对SARS-CoV-2的免疫原性，并为进一步的实验验证提供支持数据。我们提出的利用MHC和TCR结构的分子对接方法可用于鉴定大多数微生物病原体的潜在表位，前提是有MHC与TCR共结晶的晶体结构。
