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蛋白激酶CK2的皮科莫拉双价抑制剂对抗β-冠状病毒复制的活性

Dylan Grenier¹, Dennis Salomon Lopez Molina², Muriel Gelin³

¹University Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de recherche en cancérologie de Lyon, Institut Convergence Plascan, 69373 Lyon, France.

European journal of medicinal chemistry

|June 7, 2025

概括

针对素激酶2 (CK2) 的新双价抑制剂显示出对SARS-CoV-2的强烈抗病毒活性. 这些选择性CK2抑制剂有效地减少了细胞模型中的病毒复制,提供了一个有前途的治疗策略.

科学领域:

生物化学生化学
病毒学病毒学
药用化学医学化学

背景情况:

素激酶2 (CK2) 在SARS-CoV-2感染中被上调.
有限的抗病毒药物针对冠状病毒感染的CK2存在.
CK2在病毒复制和病变发生过程中发挥作用.

研究的目的:

开发高效和选择性的CK2双价抑制剂.
评估新型CK2抑制剂对SARS-CoV-2的抗病毒活性.
评估这些抑制剂的选择性和作用机制.

主要方法:

使用CX-4945作为杆的双价CK2抑制剂的设计和合成.
在体外激酶抑制试验测试以确定功效和选择性.
在细胞系 (HEK-ACE2-TMPRSS2,Vero) 和人鼻上皮细胞中进行抗病毒检测.
选择性分析与酶组的选择性分析.

主要成果:

一种双价抑制剂,Biv5,证明了亚纳米CK2抑制.
在多个细胞模型中,Biv5对SARS-CoV-2表现出强大的抗病毒活性.
在ex vivo人类鼻上皮细胞中观察到病毒复制的显著减少.
针对CK2αD口袋的准为CK2赋予了CK2的高选择性.

结论:

对CK2的双相抑制是开发SARS-CoV-2抗病毒药物的可行策略.
Biv5是一种强效和选择性的CK2抑制剂,具有显著的抗病毒功效.
需要进一步研究CK2抑制剂作为冠状病毒感染治疗药物.

关键词:

双对应抑制剂的抑制剂.凯赛因激酶 2 2 酶新冠病毒新冠病毒新冠病毒.有一个神秘的口袋.链接器链接器

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