In Silico Design and Evaluation of a Novel Therapeutic Agent Against the Spike Protein as a Novel Treatment Strategy for COVID-19 Treatment.

Q3 Biochemistry, Genetics and Molecular Biology
Soroush Sarmadi, Mohammad Reza Rahbar, Hamideh Najafi, Onyeka S Chukwudozie, Mohammad Hossein Morowvat
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引用次数: 0

Abstract

Background: Coronavirus disease 2019 (COVID-19) is a viral respiratory disease that is associated with severe damage to other human organs. It causes by a novel coronavirus, and it is spreading all over the world. To date, there is some approved vaccine or therapeutic agent which could be effective against this disease. But their effectiveness against mutated strains is not studied completely. The spike glycoprotein on the surface of the coronaviruses gives the virus the ability to bind to host cell receptors and enter cells. Inhibition of attachment of these spikes can lead to virus neutralization by inhibiting viral entrance.

Aims: In this study, we tried to use the virus entrance strategy against itself by utilizing virus receptor (ACE-2) in order to design an engineered protein consisting of a human Fc antibody fragment and a part of ACE-2, which reacts with virus RBD, and we also evaluated this interaction by computational methods and in silico methods. Subsequently, we have designed a new protein structure to bind with this site and inhibit the virus from attaching to its cell receptor, mechanically or chemically.

Methods: Various in silico software, bioinformatics, and patent databases were used to retrieve the requested gene and protein sequences. The physicochemical properties and possibility of allergenicity were also examined. Three-dimensional structure prediction and molecular docking were also performed to develop the most suitable therapeutic protein.

Results: The designed protein consisted of a total of 256 amino acids with a molecular weight of 28984.62 and 5.92 as a theoretical isoelectric point. Instability and aliphatic index and grand average of hydropathicity are 49.99, 69.57 and -0.594, respectively.

Conclusions: In silico studies can provide a good opportunity to study viral proteins and new drugs or compounds since they do not need direct exposure to infectious agents or equipped laboratories. The suggested therapeutic agent should be further characterized in vitro and in vivo.

针对尖峰蛋白的新型治疗剂的硅学设计与评估,作为治疗 COVID-19 的新型治疗策略。
背景:冠状病毒病 2019(COVID-19)是一种病毒性呼吸道疾病,会对人体其他器官造成严重损害。它由一种新型冠状病毒引起,目前正在全球蔓延。迄今为止,有一些已获批准的疫苗或治疗剂可以有效预防这种疾病。但它们对变异毒株的有效性还没有完全研究清楚。冠状病毒表面的尖头糖蛋白使病毒能够与宿主细胞受体结合并进入细胞。目的:在这项研究中,我们试图利用病毒受体(ACE-2)来对抗病毒的进入策略,从而设计出一种由人类 Fc 抗体片段和 ACE-2 的一部分组成的工程蛋白,它能与病毒 RBD 发生反应,我们还通过计算方法和硅学方法对这种相互作用进行了评估。随后,我们设计了一种新的蛋白质结构,与该位点结合,通过机械或化学方法抑制病毒附着到细胞受体上:方法:我们使用了各种硅学软件、生物信息学和专利数据库来检索所需的基因和蛋白质序列。此外,还研究了理化性质和过敏性的可能性。此外,还进行了三维结构预测和分子对接,以开发最合适的治疗蛋白:所设计的蛋白质由 256 个氨基酸组成,分子量为 28984.62,理论等电点为 5.92。不稳定性和脂肪指数及水合平均值分别为 49.99、69.57 和 -0.594:硅学研究为研究病毒蛋白质和新药物或化合物提供了一个良好的机会,因为它们不需要直接接触传染性病原体,也不需要配备实验室。建议的治疗药物应在体外和体内进一步表征。
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
Recent patents on biotechnology
Recent patents on biotechnology Biochemistry, Genetics and Molecular Biology-Biotechnology
CiteScore
2.90
自引率
0.00%
发文量
51
期刊介绍: Recent Patents on Biotechnology publishes review articles by experts on recent patents on biotechnology. A selection of important and recent patents on biotechnology is also included in the journal. The journal is essential reading for all researchers involved in all fields of biotechnology.
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