Department of Biochemistry, Bahauddin Zakariya University, Multan, 66000, Punjab, Pakistan.
Department of Animal Science, Federal University of Ceara, Fortaleza, Brazil.
Biotechnol Lett. 2024 Nov 25;47(1):2. doi: 10.1007/s10529-024-03543-7.
Guanarito mammarenavirus (GTOV) is a highly pathogenic virus that leads to Venezuelan hemorrhagic fever (VHF). Despite being a severe disease, there are currently no commercially available drugs or vaccines for its prevention.
Here we computationally formulated a mRNA vaccine construct (VC) from the genome of GTOV to produce immunity against its infections. Two proteins, namely zinc-finger motif protein (NP_899220.1), and nucleocapsid protein (NP_899211.1) were screened as potential candidates for downstream analysis.
We determined the T and B cell epitopes of the candidate proteins. The resulting epitopes were analyzed, and the best epitopes were utilized in the formation of the peptide vaccine construct. The secondary and tertiary structures of the peptide construct were predicted and validated. Docking was conducted to check the binding energy of the designed peptide vaccine with the human immune receptors, namely TLR2 and TLR4. Our designed vaccine showed stable interactions with the HLA molecules, as verified through normal mode and MD simulation analysis. The immune simulation results indicated a positive immune response against the construct. A potentially stable mRNA vaccine was formulated by adding of sequences such as the Kozak, Goblin 5' UTR, tPA-signal peptide, MITD, 3' UTRs, and a poly(A) tail to the peptide vaccine construct. Lastly, the expression probability of the mRNA vaccine was confirmed in the expression system of E. coli strain K12.
The designed vaccine showed the potential to elicit an immune response against the GTOV infection; however, experimental validation is recommended to verify the in-silico findings of this study.
瓜纳里托病毒（Guanarito mammarenavirus，GTOV）是一种高致病性病毒，可导致委内瑞拉出血热（Venezuelan hemorrhagic fever，VHF）。尽管是一种严重的疾病，但目前尚无预防该病毒的商业可用药物或疫苗。
本研究从 GTOV 基因组出发，通过计算方式构建了一种 mRNA 疫苗构建体（VC），以产生针对其感染的免疫力。筛选了两种蛋白质，即锌指结构蛋白（NP_899220.1）和核衣壳蛋白（NP_899211.1），作为下游分析的潜在候选物。
我们确定了候选蛋白的 T 细胞和 B 细胞表位。分析了得到的表位，并将最佳表位用于形成肽疫苗构建体。预测并验证了肽构建体的二级和三级结构。进行对接以检查设计的肽疫苗与人类免疫受体 TLR2 和 TLR4 的结合能。我们设计的疫苗与 HLA 分子表现出稳定的相互作用，通过正常模式和 MD 模拟分析得到验证。免疫模拟结果表明对该构建体产生了积极的免疫反应。通过向肽疫苗构建体中添加 Kozak、Goblin 5'UTR、tPA 信号肽、MITD、3'UTR 和 poly(A) 尾巴等序列，形成了一种潜在稳定的 mRNA 疫苗。最后，在大肠杆菌 K12 表达系统中证实了 mRNA 疫苗的表达概率。
设计的疫苗显示出诱导针对 GTOV 感染的免疫反应的潜力；然而，建议进行实验验证以验证本研究的计算机模拟结果。
