College of Life Science and Technology, Guangxi University, Nanning, P. R. China.
Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad, Pakistan.
PLoS One. 2020 Dec 22;15(12):e0244176. doi: 10.1371/journal.pone.0244176. eCollection 2020.
Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory coronavirus 2 (SARS-COV-2) is a significant threat to global health security. Till date, no completely effective drug or vaccine is available to cure COVID-19. Therefore, an effective vaccine against SARS-COV-2 is crucially needed. This study was conducted to design an effective multiepitope based vaccine (MEV) against SARS-COV-2. Seven highly antigenic proteins of SARS-COV-2 were selected as targets and different epitopes (B-cell and T-cell) were predicted. Highly antigenic and overlapping epitopes were shortlisted. Selected epitopes indicated significant interactions with the HLA-binding alleles and 99.93% coverage of the world's population. Hence, 505 amino acids long MEV was designed by connecting 16 MHC class I and eleven MHC class II epitopes with suitable linkers and adjuvant. MEV construct was non-allergenic, antigenic, stable and flexible. Furthermore, molecular docking followed by molecular dynamics (MD) simulation analyses, demonstrated a stable and strong binding affinity of MEV with human pathogenic toll-like receptors (TLR), TLR3 and TLR8. Finally, MEV codons were optimized for its in silico cloning into Escherichia coli K-12 system, to ensure its increased expression. Designed MEV in present study could be a potential candidate for further vaccine production process against COVID-19. However, to ensure its safety and immunogenic profile, the proposed MEV needs to be experimentally validated.
新型冠状病毒病（COVID-19）大流行是由严重急性呼吸系统综合征冠状病毒 2（SARS-COV-2）引起的，是对全球卫生安全的重大威胁。迄今为止，尚无治愈 COVID-19 的完全有效药物或疫苗。因此，急需针对 SARS-COV-2 的有效疫苗。本研究旨在设计针对 SARS-COV-2 的有效多表位疫苗（MEV）。选择了七种具有高度抗原性的 SARS-COV-2 蛋白作为靶标，并预测了不同的表位（B 细胞和 T 细胞）。高抗原性和重叠表位被列为候选。选定的表位与 HLA 结合等位基因有显著的相互作用，能覆盖全球 99.93%的人群。因此，通过连接 16 个 MHC Ⅰ类和 11 个 MHC Ⅱ类表位与合适的接头和佐剂，设计了 505 个氨基酸长的 MEV。MEV 构建体无变应原性、抗原性、稳定性和灵活性。此外，分子对接后进行分子动力学（MD）模拟分析，表明 MEV 与人病原体 Toll 样受体（TLR）、TLR3 和 TLR8 具有稳定且强的结合亲和力。最后，对 MEV 密码子进行优化，以便在大肠杆菌 K-12 系统中进行计算机克隆，以确保其表达增加。本研究设计的 MEV 可能是进一步开发针对 COVID-19 的疫苗的潜在候选物。然而，为确保其安全性和免疫原性，需要对所提出的 MEV 进行实验验证。
