鉴定对病毒包膜糖蛋白有活性的人类蛋白酶的生物信息学方法:关于 SARS-CoV-2 Spike 蛋白的案例研究

IF 1.5 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Biology Pub Date : 2024-04-09 DOI:10.1134/s0026893324020122
E. V. Matveev, G. V. Ponomarev, M. D. Kazanov
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引用次数: 0

摘要

摘要--包括造成 COVID-19 大流行的冠状病毒 SARS-CoV-2 在内的许多病毒都是通过细胞-病毒膜融合过程进入宿主细胞的,而这一过程是由蛋白水解酶激活的。通常,这些酶是宿主细胞蛋白酶。识别激活病毒的蛋白酶并不是一项简单的任务,但对于开发新的抗病毒药物非常重要。在这项研究中,我们开发了一种生物信息学方法,用于识别能裂解病毒包膜糖蛋白的蛋白酶。所提出的方法包括使用人类蛋白酶底物特异性的预测模型,以及应用结构分析方法,根据蛋白质的三维结构预测蛋白质区域易被蛋白水解的程度。利用已知底物的信息为 169 种人类蛋白酶构建了特异性模型。与特异性模型同时应用的还有之前开发的潜在蛋白水解位点结构分析方法。对 SARS-CoV-2 尖峰蛋白进行了验证,对其蛋白水解位点进行了深入研究。
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A Bioinformatics Method for Identification of Human Proteases Active against Viral Envelope Glycoproteins: A Case Study on the SARS-CoV-2 Spike Protein

Abstract—Many viruses, including SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, enter host cells through a process of cell-viral membrane fusion that is activated by proteolytic enzymes. Typically, these enzymes are host cell proteases. Identifying the proteases that activate the virus is not a simple task but is important for the development of new antiviral drugs. In this study, we developed a bioinformatics method for identifying proteases that can cleave viral envelope glycoproteins. The proposed approach involves the use of predictive models for the substrate specificity of human proteases and the application of a structural analysis method for predicting the vulnerability of protein regions to proteolysis based on their 3D structures. Specificity models were constructed for 169 human proteases using information on their known substrates. A previously developed method for structural analysis of potential proteolysis sites was applied in parallel with specificity models. Validation of the proposed approach was performed on the SARS-CoV-2 spike protein, whose proteolysis sites have been well studied.

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来源期刊
Molecular Biology
Molecular Biology 生物-生化与分子生物学
CiteScore
1.30
自引率
8.30%
发文量
78
审稿时长
3 months
期刊介绍: Molecular Biology is an international peer reviewed journal that covers a wide scope of problems in molecular, cell and computational biology including genomics, proteomics, bioinformatics, molecular virology and immunology, molecular development biology, molecular evolution and related areals. Molecular Biology publishes reviews, experimental and theoretical works. Every year, the journal publishes special issues devoted to most rapidly developing branches of physical-chemical biology and to the most outstanding scientists.
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