Computer-aided rational design of a mRNA vaccine against Guanarito mammarenavirus.

IF 2 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Biotechnology Letters Pub Date : 2024-11-25 DOI:10.1007/s10529-024-03543-7

Mohibullah Shah, Asifa Sarfraz, Muhammad Shehroz, Asia Perveen, Samavia Jaan, Aqal Zaman, Umar Nishan, Arlindo A Moura, Riaz Ullah, Zafar Iqbal, Mohamed A Ibrahim

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Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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通过计算机辅助合理设计 mRNA 疫苗，预防瓜纳里托乳头瘤病毒。

目的：Guanarito mammarenavirus（GTOV）是一种导致委内瑞拉出血热（VHF）的高致病性病毒。方法：在此，我们通过计算从 GTOV 基因组中提取了一种 mRNA 疫苗构建体（VC），以产生对其感染的免疫力。方法：我们通过计算从 GTOV 的基因组中构建了 mRNA 疫苗构建体（VC），并筛选了两种蛋白，即锌指基序蛋白（NP_899220.1）和核噬菌体蛋白（NP_899211.1），作为下游分析的潜在候选蛋白：结果：我们确定了候选蛋白的 T 细胞和 B 细胞表位。结果：我们确定了候选蛋白的 T 细胞和 B 细胞表位，并对所得表位进行了分析，利用最佳表位构建了多肽疫苗。预测并验证了多肽构建体的二级和三级结构。对设计的多肽疫苗与人类免疫受体（即 TLR2 和 TLR4）的结合能进行了对接。通过正常模式和 MD 模拟分析，验证了我们设计的疫苗与 HLA 分子之间存在稳定的相互作用。免疫模拟结果表明，该构建体能产生积极的免疫反应。通过在多肽疫苗构建体中添加 Kozak、Goblin 5'UTR、tPA 信号肽、MITD、3'UTR 和 poly(A) 尾部等序列，配制出了潜在稳定的 mRNA 疫苗。最后，在大肠杆菌 K12 菌株的表达系统中确认了 mRNA 疫苗的表达概率：结论：所设计的疫苗显示出引起针对 GTOV 感染的免疫反应的潜力；然而，建议进行实验验证，以验证本研究的室内发现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biotechnology Letters 工程技术-生物工程与应用微生物

CiteScore

5.90

自引率

3.70%

发文量

108

审稿时长

1.2 months

期刊介绍： Biotechnology Letters is the world’s leading rapid-publication primary journal dedicated to biotechnology as a whole – that is to topics relating to actual or potential applications of biological reactions affected by microbial, plant or animal cells and biocatalysts derived from them. All relevant aspects of molecular biology, genetics and cell biochemistry, of process and reactor design, of pre- and post-treatment steps, and of manufacturing or service operations are therefore included. Contributions from industrial and academic laboratories are equally welcome. We also welcome contributions covering biotechnological aspects of regenerative medicine and biomaterials and also cancer biotechnology. Criteria for the acceptance of papers relate to our aim of publishing useful and informative results that will be of value to other workers in related fields. The emphasis is very much on novelty and immediacy in order to justify rapid publication of authors’ results. It should be noted, however, that we do not normally publish papers (but this is not absolute) that deal with unidentified consortia of microorganisms (e.g. as in activated sludge) as these results may not be easily reproducible in other laboratories. Papers describing the isolation and identification of microorganisms are not regarded as appropriate but such information can be appended as supporting information to a paper. Papers dealing with simple process development are usually considered to lack sufficient novelty or interest to warrant publication.