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In silico investigation of the viroporin E as a vaccine target against SARS-CoV-2

机译:在血管素e作为针对SARS-COV-2的疫苗靶标的硅研究

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Viroporins, integral viral membrane ion channel proteins, interact with host-cell proteins deregulating physiological processes and activating inflammasomes. Severity of COVID-19 might be associated with hyperinflammation, thus we aimed at the complete immunoinformatic analysis of the SARS-CoV-2 viroporin E, PODTC4. We also identified the human proteins interacting with PODTC4 and the enriched molecular functions of the corresponding genes. The complete sequence of PODTC4 in FASTA format was processed in 10 databases relative to secondary and tertiary protein structure analyses and prediction of optimal vaccine epitopes. Three more databases were accessed for the retrieval and the molecular functional characterization of the PODTC4 human interactors. The immunoinformatics analysis resulted in the identification of 4 discontinuous B-cell epitopes along with 1 linear B-cell epitope and 11 T-cell epitopes which were found to be antigenic, immunogenic, nonallergen, nontoxin, and unable to induce autoimmunity thus fulfilling prerequisites for vaccine design. The functional enrichment analysis showed that the predicted host interactors of PODTC4 target the cellular acetylation network. Two of the identified host-cell proteins - BRD2 and BRD4 - have been shown to be promising targets for antiviral therapy. Thus, our findings have implications for COVID-19 therapy and indicate that viroporin E could serve as a promising vaccine target against SARS-CoV-2. Validation experiments are required to complement these in silico results.
机译:病毒蛋白是完整的病毒膜离子通道蛋白,与宿主细胞蛋白相互作用,解除生理过程的调节,激活炎症体。2019冠状病毒疾病的严重程度可能与炎症反应有关,因此我们针对SARS COV-2病毒载体E、PODTC4的完整免疫信息学分析。我们还鉴定了与PODTC4相互作用的人类蛋白质以及相应基因的丰富分子功能。与二级和三级蛋白质结构分析和最佳疫苗表位预测相关的10个数据库中处理了FASTA格式的PODTC4完整序列。为了检索PODTC4人类相互作用物并对其进行分子功能表征,又访问了三个数据库。通过免疫信息学分析,鉴定出4个不连续的B细胞表位、1个线性B细胞表位和11个T细胞表位,这些表位具有抗原性、免疫原性、非抗原性、非毒素性,并且不能诱导自身免疫,因此满足了疫苗设计的先决条件。功能富集分析表明,预测的PODTC4宿主相互作用物以细胞乙酰化网络为靶点。已确定的两种宿主细胞蛋白——BRD2和BRD4——已被证明是抗病毒治疗的有希望的靶点。因此,我们的2019冠状病毒疾病的研究结果表明,ViROP溶素E可以作为一种很有前途的针对SARS COV-2的疫苗靶标。需要验证实验来补充这些电子结果。

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