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通过探索 MERS-COV 蛋白质组学对多表位基于亚单位疫苗的合理设计:反向疫苗学和分子对接方法。

Rational design of multi epitope-based subunit vaccine by exploring MERS-COV proteome: Reverse vaccinology and molecular docking approach.

机构信息

Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan.

Department of Chemistry, Government College University, Faisalabad, Pakistan.

出版信息

PLoS One. 2021 Feb 3;16(2):e0245072. doi: 10.1371/journal.pone.0245072. eCollection 2021.

Abstract

Middle East respiratory syndrome (MERS-COV), first identified in Saudi Arabia, was caused by a novel strain of coronavirus. Outbreaks were recorded from different regions of the world, especially South Korea and the Middle East, and were correlated with a 35% mortality rate. MERS-COV is a single-stranded, positive RNA virus that reaches the host by binding to the receptor of dipeptidyl-peptides. Because of the unavailability of the vaccine available for the protection from MERS-COV infection, the rapid case detection, isolation, infection prevention has been recommended to combat MERS-COV infection. So, vaccines for the treatment of MERS-COV infection need to be developed urgently. A possible antiviral mechanism for preventing MERS-CoV infection has been considered to be MERS-CoV vaccines that elicit unique T-cell responses. In the present study, we incorporated both molecular docking and immunoinformatic approach to introduce a multiepitope vaccine (MEP) against MERS-CoV by selecting 15 conserved epitopes from seven viral proteins such as three structural proteins (envelope, membrane, and nucleoprotein) and four non-structural proteins (ORF1a, ORF8, ORF3, ORF4a). The epitopes, which were examined for non-homologous to host and antigenicity, were selected on the basis of conservation between T-cell, B-cell, and IFN-γ epitopes. The selected epitopes were then connected to the adjuvant (β-defensin) at the N-terminal through an AAY linker to increase the immunogenic potential. Structural modelling and physiochemical characteristic were applied to the vaccine construct developed. Afterwards the structure has been successfully docked with antigenic receptor, Toll-like receptor 3 (TLR-3) and in-silico cloning ensures that its expression efficiency is legitimate. Nonetheless the MEP presented needs tests to verify its safety and immunogenic profile.

摘要

中东呼吸综合征冠状病毒(MERS-CoV)最初在沙特阿拉伯被发现,是由一种新型冠状病毒引起的。世界不同地区(尤其是韩国和中东地区)都有疫情记录,死亡率为 35%。MERS-CoV 是一种单链、正链 RNA 病毒,通过与二肽基肽酶的受体结合到达宿主。由于目前尚无针对 MERS-CoV 感染的可用疫苗,因此建议快速检测病例、隔离和感染预防,以对抗 MERS-CoV 感染。因此,急需开发针对 MERS-COV 感染的疫苗。一种可能的预防 MERS-CoV 感染的抗病毒机制被认为是能引起独特 T 细胞反应的 MERS-CoV 疫苗。在本研究中,我们结合了分子对接和免疫信息学方法,通过从七种病毒蛋白(包括三种结构蛋白[包膜、膜和核蛋白]和四种非结构蛋白[ORF1a、ORF8、ORF3 和 ORF4a])中选择 15 个保守表位,提出了一种针对 MERS-CoV 的多表位疫苗(MEP)。基于 T 细胞、B 细胞和 IFN-γ 表位之间的保守性,选择了对宿主无同源性和抗原性的表位。然后,将所选表位通过 AAY 接头与 N 端的佐剂(β-防御素)连接,以提高免疫原性。对接过程中对疫苗构建体进行了结构建模和理化特性分析。随后成功对接了抗原受体 Toll 样受体 3(TLR-3),并通过计算机模拟克隆确保其表达效率合理。尽管如此,仍需要对所提出的 MEP 进行测试,以验证其安全性和免疫原性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6895/7857617/79df33122e46/pone.0245072.g001.jpg

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