一个内在的循环介导的结构稳定性调节SADS-CoV和SARS-CoV-2主要蛋白酶中的抑制剂功效
Rui Zeng1, Shizhan Cui2, Xiaoyan Xia1
1National Clinical Research Center for Geriatrics, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
PLoS pathogens
|February 24, 2026
概括
确定了猪急性腹综合征冠状病毒 (SADS-CoV) 主蛋白酶结构,揭示了一个新的抑制机制. 这一发现有助于开发针对SADS-CoV的向抗病毒疗法,SADS-CoV是一个重要的动物性传染病原体.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 药物发现 药物发现 药物发现
背景情况:
- 猪急性腹综合征冠状病毒 (SADS-CoV) 构成了相当大的动物感染威胁.
- 缺少SADS-CoV主要蛋白酶 (Mpro) 的结构数据阻碍了抗病毒药物开发.
研究的目的:
- 阐明SADS-CoV Mpro及其复合物与抑制剂的高分辨率结构.
- 了解新的抑制机制和抑制剂功能的结构基础.
主要方法:
- 使用X射线晶体学来确定SADS-CoV Mpro及其抑制剂复合物的结构.
- 基于细胞的测定和猪肠道器官被用来评估抗病毒活性.
主要成果:
- 获得了SADS-CoV Mpro与抑制剂27h和SY110的高分辨率结构,揭示了独特的单螺旋形状 (残留物40-53).
- 这与SARS-CoV-2 Mpro中的卷轴结构不同,影响了抑制剂的功效.
- 抑制剂27h在体外和器官中有效抑制了SADS-CoV复制.
结论:
- 内在的Mpro动力学显著影响抑制剂的功效.
- 在Alphacoronavirus Mpros中缺少'51'残留物对于观察到的形状变化至关重要.
- 这些发现为设计针对冠状病毒的广谱Mpro抑制剂提供了基础.
相关概念视频
Structural Protein Function
3.3K
3.3K
Structural Protein Function
30.2K
Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to...
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to...
30.2K
Covalently Linked Protein Regulators
9.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
9.8K
Covalently Linked Protein Regulators
2.1K
2.1K
Enzyme Inhibition
93.3K
Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
93.3K
Single-Strand DNA Binding Proteins
17.0K
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
17.0K


