Use of in silico approaches, synthesis and profiling of Pan-filovirus GP-1,2 preprotein specific antibodies.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Maciej Wiśniewski, Peace Babirye, Carol Musubika, Eleni Papakonstantinou, Samuel Kirimunda, Michał Łaźniewski, Teresa Szczepińska, Moses L. Joloba, Elias Eliopoulos, Erik Bongcam-Rudloff, D. Vlachakis, Anup Kumar Halder, Dariusz Plewczyński, M. Wayengera
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Abstract

Intermolecular interactions of protein-protein complexes play a principal role in the process of discovering new substances used in the diagnosis and treatment of many diseases. Among such complexes of proteins, we have to mention antibodies; they interact with specific antigens of two genera of single-stranded RNA viruses belonging to the family Filoviridae-Ebolavirus and Marburgvirus; both cause rare but fatal viral hemorrhagic fever in Africa, with pandemic potential. In this research, we conduct studies aimed at the design and evaluation of antibodies targeting the filovirus glycoprotein precursor GP-1,2 to develop potential targets for the pan-filovirus easy-to-use rapid diagnostic tests. The in silico research using the available 3D structure of the natural antibody-antigen complex was carried out to determine the stability of individual protein segments in the process of its formation and maintenance. The computed free binding energy of the complex and its decomposition for all amino acids allowed us to define the residues that play an essential role in the structure and indicated the spots where potential antibodies can be improved. Following that, the study involved targeting six epitopes of the filovirus GP1,2 with two polyclonal antibodies (pABs) and 14 monoclonal antibodies (mABs). The evaluation conducted using Enzyme Immunoassays tested 62 different sandwich combinations of monoclonal antibodies (mAbs), identifying 10 combinations that successfully captured the recombinant GP1,2 (rGP). Among these combinations, the sandwich option (3G2G12* - (rGP) - 2D8F11) exhibited the highest propensity for capturing the rGP antigen.
使用硅学方法合成和分析泛非病毒 GP-1,2 前蛋白特异性抗体。
在发现用于诊断和治疗多种疾病的新物质的过程中,蛋白质-蛋白质复合物的分子间相互作用发挥着主要作用。在这些蛋白质复合物中,我们不得不提到抗体;它们与属于丝状病毒科-埃博拉病毒属和马尔堡病毒属的两种单链 RNA 病毒的特定抗原相互作用。本研究旨在设计和评估针对丝状病毒糖蛋白前体 GP-1,2 的抗体,为泛丝状病毒简易快速诊断检测开发潜在靶标。利用现有的天然抗体-抗原复合物的三维结构进行了硅学研究,以确定单个蛋白质片段在其形成和维持过程中的稳定性。通过计算复合物的自由结合能及其对所有氨基酸的分解,我们确定了在结构中起重要作用的残基,并指出了潜在抗体可以改进的地方。随后,我们用两种多克隆抗体(pABs)和 14 种单克隆抗体(mABs)对丝状病毒 GP1,2 的六个表位进行了靶向研究。使用酶联免疫法进行的评估测试了 62 种不同的单克隆抗体(mAbs)夹心组合,确定了 10 种能成功捕获重组 GP1,2 (rGP)的组合。在这些组合中,夹心方案(3G2G12* - (rGP) - 2D8F11)捕获 rGP 抗原的倾向性最高。
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
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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