人副流感病毒-3 CD4+ T细胞表位的计算机预测和评价。

IF 1.5 4区 医学 Q4 CHEMISTRY, MEDICINAL Current computer-aided drug design Pub Date : 2023-01-01 DOI:10.2174/1573409919666221205122633
Peyman Bemani, Mozafar Mohammadi
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引用次数: 0

摘要

背景:人类副流感病毒3型(HPIV-3)通过细支气管炎和肺炎是下呼吸道感染的常见原因。它是婴幼儿住院的主要原因,也是免疫功能受损和移植患者发病和死亡的主要原因之一。尽管做出了许多努力,但目前还没有专门的抗hpiv -3药物或经批准的疫苗来预防和控制这种病毒。鉴定具有与人类白细胞抗原(HLA) II类分子结合能力的HPIV-3表位有助于设计新的HPIV-3感染候选疫苗,也可用于移植和免疫功能低下患者的HPIV-3特异性T细胞的体外刺激和增殖。目的:从四种主要HPIV-3抗原预测和综合评价CD4+T细胞表位(HLA-II结合物)。方法:利用生物和免疫信息学软件,从融合蛋白(F)、血凝素神经氨酸酶(HN)、核衣壳(N)和基质(M)蛋白等四种主要HPIV-3抗原预测并综合评价CD4+T细胞表位(HLA-II结合物)。对预测表位的毒性、致敏性、Blast筛选和人群覆盖率进行了评价。通过对接研究评估最终选择的表位的结合能力。结果:经过blast筛选、毒性和致敏性试验、人群覆盖、对接研究等筛选步骤,最终筛选出9个候选表位。选择的表位具有较高的群体覆盖率,对接研究显示与阴性对照肽相比,最终表位的结合亲和力显著更高。结论:最终选择的抗原表位可用于候选疫苗的设计以及免疫功能低下个体和移植患者的治疗。
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In silico Prediction and Evaluation of Human Parainfluenza Virus-3 CD4+ T Cell Epitopes.

Background: Human parainfluenza viruses type 3 (HPIV-3) through bronchiolitis and pneumonia is a common cause of lower respiratory tract infections. It is the main cause of hospitalization of infants and young children and also one of the main causes of morbidity and mortality in immuno-compromised and transplant patients. Despite many efforts, there is currently no specific anti-HPIV-3 drug or approved vaccine to prevent and control the virus. Identification of HPIV-3 epitopes with the capability of binding to human leukocyte antigen (HLA) class II molecules can be helpful in designing new vaccine candidates against HPIV-3 infection, and also can be useful for the in vitro stimulation and proliferation of HPIV-3-specific T cells for transplant and immunocompromised patients.

Objective: To predict and comprehensively evaluate CD4+T cell epitope (HLA-II binders) from four main HPIV-3 antigens.

Methods: In the present work, we predicted and comprehensively evaluated CD4+T cell epitope (HLA-II binders) from four main HPIV-3 antigens, including fusion protein (F), hemagglutininneuraminidase (HN), nucleocapsid (N) and matrix (M) proteins using bio- and immunoinformatics software. The toxicity, allergenicity, Blast screening and population coverage of the predicted epitopes were evaluated. The binding ability of the final selected epitopes was evaluated via a docking study.

Results: After several filtering steps, including blast screening, toxicity and allergenicity assay, population coverage and docking study, 9 epitopes were selected as candidate epitopes. The selected epitopes showed high population coverage and docking studies revealed a significantly higher binding affinity for the final epitopes in comparison with the negative control peptides.

Conclusion: The final selected epitopes could be useful in designing vaccine candidates and for the treatment of immune-compromised individuals and patients with transplantation.

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来源期刊
Current computer-aided drug design
Current computer-aided drug design 医学-计算机:跨学科应用
CiteScore
3.70
自引率
5.90%
发文量
46
审稿时长
>12 weeks
期刊介绍: Aims & Scope Current Computer-Aided Drug Design aims to publish all the latest developments in drug design based on computational techniques. The field of computer-aided drug design has had extensive impact in the area of drug design. Current Computer-Aided Drug Design is an essential journal for all medicinal chemists who wish to be kept informed and up-to-date with all the latest and important developments in computer-aided methodologies and their applications in drug discovery. Each issue contains a series of timely, in-depth reviews, original research articles and letter articles written by leaders in the field, covering a range of computational techniques for drug design, screening, ADME studies, theoretical chemistry; computational chemistry; computer and molecular graphics; molecular modeling; protein engineering; drug design; expert systems; general structure-property relationships; molecular dynamics; chemical database development and usage etc., providing excellent rationales for drug development.
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