Department of Microbiology and Molecular Genetics, Faculty of Life Sciences, University of Okara, Okara, Pakistan.
Department of Ear, Nose, and Throat (ENT), District Headquarter (DHQ) Teaching Hospital Faisalabad, Faisalabad, Punjab, Pakistan.
Front Cell Infect Microbiol. 2023 May 24;13:1134802. doi: 10.3389/fcimb.2023.1134802. eCollection 2023.
There has been progressive improvement in immunoinformatics approaches for epitope-based peptide design. Computational-based immune-informatics approaches were applied to identify the epitopes of SARS-CoV-2 to develop vaccines. The accessibility of the SARS-CoV-2 protein surface was analyzed, and hexa-peptide sequences (KTPKYK) were observed having a maximum score of 8.254, located between amino acids 97 and 102, whereas the FSVLAC at amino acids 112 to 117 showed the lowest score of 0.114. The surface flexibility of the target protein ranged from 0.864 to 1.099 having amino acid ranges of 159 to 165 and 118 to 124, respectively, harboring the FCYMHHM and YNGSPSG hepta-peptide sequences. The surface flexibility was predicted, and a 0.864 score was observed from amino acids 159 to 165 with the hepta-peptide (FCYMHHM) sequence. Moreover, the highest score of 1.099 was observed between amino acids 118 and 124 against YNGSPSG. B-cell epitopes and cytotoxic T-lymphocyte (CTL) epitopes were also identified against SARS-CoV-2. In molecular docking analyses, -0.54 to -26.21 kcal/mol global energy was observed against the selected CTL epitopes, exhibiting binding solid energies of -3.33 to -26.36 kcal/mol. Based on optimization, eight epitopes (SEDMLNPNY, GSVGFNIDY, LLEDEFTPF, DYDCVSFCY, GTDLEGNFY, QTFSVLACY, TVNVLAWLY, and TANPKTPKY) showed reliable findings. The study calculated the associated HLA alleles with MHC-I and MHC-II and found that MHC-I epitopes had higher population coverage (0.9019% and 0.5639%) than MHC-II epitopes, which ranged from 58.49% to 34.71% in Italy and China, respectively. The CTL epitopes were docked with antigenic sites and analyzed with MHC-I HLA protein. In addition, virtual screening was conducted using the ZINC database library, which contained 3,447 compounds. The 10 top-ranked scrutinized molecules (ZINC222731806, ZINC077293241, ZINC014880001, ZINC003830427, ZINC030731133, ZINC003932831, ZINC003816514, ZINC004245650, ZINC000057255, and ZINC011592639) exhibited the least binding energy (-8.8 to -7.5 kcal/mol). The molecular dynamics (MD) and immune simulation data suggest that these epitopes could be used to design an effective SARS-CoV-2 vaccine in the form of a peptide-based vaccine. Our identified CTL epitopes have the potential to inhibit SARS-CoV-2 replication.
免疫信息学方法在基于表位的肽设计方面取得了逐步进展。应用基于计算的免疫信息学方法来鉴定 SARS-CoV-2 的表位，以开发疫苗。分析了 SARS-CoV-2 蛋白表面的可达性，并观察到六肽序列（KTPKYK）的最大得分为 8.254，位于氨基酸 97 和 102 之间，而氨基酸 112 到 117 的 FSVLAC 得分为最低的 0.114。目标蛋白的表面柔性范围为 0.864 至 1.099，氨基酸范围分别为 159 至 165 和 118 至 124，分别含有 FCYMHHM 和 YNGSPSG 七肽序列。预测了表面柔性，在氨基酸 159 至 165 处观察到 0.864 的得分，其序列为 FCYMHHM。此外，在氨基酸 118 至 124 处观察到最高得分为 1.099，对应 YNGSPSG。还鉴定了 SARS-CoV-2 的 B 细胞表位和细胞毒性 T 淋巴细胞（CTL）表位。在分子对接分析中，针对选定的 CTL 表位观察到-0.54 至-26.21 kcal/mol 的全局能量，表现出-3.33 至-26.36 kcal/mol 的结合固能。经过优化，发现了 8 个表位（SEDMLNPNY、GSVGFNIDY、LLEDEFTPF、DYDCVSFCY、GTDLEGNFY、QTFSVLACY、TVNVLAWLY 和 TANPKTPKY）具有可靠的发现。该研究计算了与 MHC-I 和 MHC-II 相关的 HLA 等位基因，并发现 MHC-I 表位具有比 MHC-II 表位更高的人群覆盖率（意大利为 0.9019%，中国为 0.5639%），分别为 58.49%至 34.71%。CTL 表位与抗原结合位点对接，并与 MHC-I HLA 蛋白进行分析。此外，使用 ZINC 数据库库进行了虚拟筛选，该库包含 3447 种化合物。排名前 10 的筛选分子（ZINC222731806、ZINC077293241、ZINC014880001、ZINC003830427、ZINC030731133、ZINC003932831、ZINC003816514、ZINC004245650、ZINC000057255 和 ZINC011592639）表现出最低的结合能（-8.8 至-7.5 kcal/mol）。分子动力学（MD）和免疫模拟数据表明，这些表位可用于设计基于肽的 SARS-CoV-2 疫苗形式的有效疫苗。我们鉴定的 CTL 表位具有抑制 SARS-CoV-2 复制的潜力。
Zotero 插件
