来自SARS-CoV-2的Mpro的结构及其抑制剂的发现
Zhenming Jin1,2, Xiaoyu Du2, Yechun Xu3
1Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Nature
|April 10, 2020
概括
研究人员迅速确定了针对SARS-CoV-2主要蛋白酶的潜在COVID-19治疗方法. 六种化合物抑制了酶,其中一种在细胞检测中显示出抗病毒活性,证明了有效的药物发现策略.
科学领域:
- 病毒学
- 药物发现
- 结构生物学
背景情况:
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 导致COVID-19,治疗选择有限.
- SARS-CoV-2 主蛋白酶 (Mpro) 对于病毒复制至关重要,也是关键的药物标.
研究的目的:
- 快速发现潜在的COVID-19治疗的化合物.
- 确定SARS-CoV-2主要蛋白酶 (Mpro) 的抑制剂.
主要方法:
- 组合结构辅助药物设计,虚拟查和高通量查.
- 测试了超过1万种Mpro抑制的化合物.
- 确定与抑制剂复合的Mpro的晶体结构.
主要成果:
- 通过计算机辅助设计确定了基于机制的抑制剂 (N3).
- 六种化合物表现出Mpro抑制,IC50值在0. 67至21. 4μM之间.
- 在基于细胞的测试中,Ebselen显示出有前途的抗病毒活性.
结论:
- 查策略有效地确定了SARS-CoV-2的药物线索.
- 这种方法可以加速新兴传染病的药物发现.
- 进一步开发已识别的化合物可能会导致临床治疗.
相关概念视频
Conjugated Proteins
26.0K
Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
26.0K
Protein-protein Interfaces
14.4K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
14.4K
Protein Organization
8.8K
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence....
The primary structure of a protein is its amino acid sequence....
8.8K


