冠状病毒复制的广谱后入境抑制剂:心脏动性类固醇和单因素
Shahrzad Jahanshahi1, Hong Ouyang2, Choudhary Ahmed3
1Dept. of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada; Dept. of Biochemistry, University of Toronto, Toronto, ON, Canada.
Virology
|November 6, 2023
概括
两种FDA批准的药物类别,心力增生类固醇 (digitoxin,ouabain) 和monensin,通过破坏受感染细胞功能,对冠状病毒 (HCoV-229E,HCoV-OC43,SARS-CoV-2) 显示出强大的抗病毒活性.
科学领域:
- 病毒学 病毒学
- 药理学 药理学是指药理学的学科.
- 细胞生物学 细胞生物学
背景情况:
- 冠状病毒 (CoV) 对公共健康构成重大威胁,需要新的治疗策略.
- 目前对Cov病毒的抗病毒治疗方法有限,这凸显了对药物的重新定位和发现的需要.
研究的目的:
- 确定抑制各种人类冠状病毒 (HCoV) 复制的小分子.
- 在相关细胞模型中研究已识别的化合物的抗病毒机制.
主要方法:
- 通过小分子的高通量选来识别HCoV复制抑制剂.
- 在初级人类鼻上皮细胞和肺器官中进行抗病毒检测.
- 对病毒基因表达 (蛋白质和RNA) 和信号通路参与的分析.
主要成果:
- 心脏动力类固醇 (数字毒素,奥阿巴因) 和离子体蒙因素强烈抑制了HCoV-229E,HCoV-OC43和SARS-CoV-2复制 (低nM EC50s).
- 化合物在原始人类细胞和器官中表现出抗病毒活性,在病毒进入后起作用.
- 滴毒素的活性涉及MEK/JNK信号传递,而单酶的活性则通过抑制某些通路而被逆转.
结论:
- 滴定毒素,奥阿巴因和蒙宁素表现出强大的抗冠状病毒特性.
- 这些FDA批准的药物通过改变受感染细胞的特性来阻止病毒复制而起作用.
- 重用这些药物提供了一个有前途的治疗途径来对抗HCoV感染.
更多相关视频
相关概念视频
Eukaryotic Transcription Inhibitors
9.8K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.8K
Viruses with RNA Genomes
34
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
34
Subviral Agents
19
Subviral agents are infectious entities that resemble viruses but lack one or more viral components, such as a capsid or essential replication machinery. These agents include viroids, prions, and satellites, each possessing distinct structural and functional characteristics that influence their mode of infection and replication.Viroids are the simplest subviral agents, consisting of circular, single-stranded RNA molecules without a protein coat. They exclusively infect plants, relying entirely...
19
Antimicrobial Effectiveness
24
The effectiveness of antimicrobial agents depends on various factors influencing their ability to eliminate microbial populations. Larger microbial populations require more time for complete eradication, emphasizing the importance of population size analysis when evaluating antimicrobial efficacy.Microbial resistance to antimicrobial agents varies significantly. Highly resilient microorganisms include endospores, gram-negative bacteria, and non-enveloped viruses, while prions are exceptionally...
24
Combined Effects of Drugs: Synergism
4.0K
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
4.0K


