阿贝马西克利布通过抑制pUL97介导的SAMHD1酸化来限制HCMV的复制
Georgios Vavouras Syrigos1, Maximilian Feige1, Alicia Dirlam1
1Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, Germany.
Antiviral research
|July 29, 2023
概括
美国食品和药物管理局批准的CDK抑制剂作为抗病毒药物对抗人类细胞巨血病毒 (HCMV) 是有前途的. 这些药物阻止病毒激酶pUL97使抗病毒因子SAMHD1失活,提供了一种新的治疗策略.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 人类细胞巨乳病毒 (HCMV) 对新生儿和免疫功能低下的人构成重大风险.
- HCMV复制涉及与宿主细胞因子的相互作用,包括循环林依赖激酶 (CDK).
- HCMV编码病毒激酶pUL97,一种CDK同类物,通过酸化对抗抗病毒因子SAMHD1.
研究的目的:
- 研究FDA批准的CDK抑制剂 (CDKI) 作为抗HCMV的抗病毒药物的治疗潜力.
- 确定CDKI是否可以防止SAMHD1.1的HCMV介导失活.
- 确定SAMHD1作为HCMV感染的治疗点.
主要方法:
- 在巨细胞中HCMV感染后SAMHD1无活化动态的分析.
- 测试CDKI对抗HCMV的抗病毒活性.
- 评估CDKI阻断pUL97介导的SAMHD1酸化的能力.
主要成果:
- 在巨细胞感染后的早期,HCMV pUL97可化并使SAMHD1失活.
- 第二代CDKI的Abemaciclib显示出对HCMV的强有力的抗病毒活性.
- 阿贝马西克利布的抗病毒作用主要归因于其抑制pUL97介导的SAMHD1酸化.
结论:
- 经过临床批准的CDKI代表了对HCMV感染的有前途的治疗途径.
- 抑制pUL97介导的SAMHD1无活化是一种可行的抗病毒策略.
- SAMHD1被确定为对抗HCMV的强大和有效的治疗标.
相关概念视频
02:23Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
02:34Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
00:50Anaphase Promoting Complex
2.9K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.9K
01:52Eukaryotic Transcription Inhibitors
9.9K
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...
9.9K