硫福拉的核因子红色素2相关因子2 (Nrf2) - 抗SARS-CoV-2活动的依赖和独立机制
Ziqi Yan1, Weifeng Liang1, Lingxiang Zhu1
1Department of Pharmacology and Toxicology, School of Pharmacy, University of Arizona, Tucson, AZ 85721, USA.
概括
Nrf2 缺乏会使SARS-CoV-2 感染恶化. 虽然硫黄 (SFN) 在细胞中表现出独立于Nrf2的抗病毒作用,但其对SARS-CoV-2的疗效依赖于Nrf2在体内.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
背景情况:
- 核因子红色素2相关因子2 (Nrf2) 对于抗氧化和抗炎反应至关重要.
- Nrf2在抗病毒防御中的作用,特别是对抗SARS-CoV-2的作用,尚不清楚.
- 现有的Nrf2激活剂显示出抗SARS-CoV-2的潜力,但机制需要澄清.
研究的目的:
- 为了研究Nrf2在SARS-CoV-2感染中的作用.
- 评估Nrf2调节器对SARS-CoV-2的抗病毒功效和机制.
- 为了确定抗病毒化合物的Nrf2依赖性.
主要方法:
- 用了两个小鼠模型进行SARS-CoV-2感染.
- 评估病毒载量和炎症标志物.
- 选了五个Nrf2调节器 (EGCG,SFN,DMF等) 对于抗病毒活性.
- 对SFN进行了蛋白酶抑制试验.
- 在体外研究中使用Nrf2淘汰细胞系.
主要成果:
- Nrf2 缺陷加剧了 SARS-CoV-2 病毒载量,并改变了小鼠的炎症反应.
- SFN,EGCG和DMF表现出显著的抗病毒作用.
- SFN是最有效的,可以抑制SARS-CoV-2主要蛋白酶 (MPro),而不会影响病毒的进入.
- 在实验室中,SFN的抗病毒活性是Nrf2独立的,但在体内Nrf2淘汰小鼠中完全失去了.
- MA30模型证实了SFN的Nrf2依赖的抗病毒功能.
结论:
- Nrf2在控制SARS-CoV-2感染和调节炎症反应方面发挥着至关重要的作用.
- 通过MPro向,SFN表现出强大的SARS-CoV-2抑制,独立于细胞培养中的Nrf2.
- Nrf2-依赖的途径对于SFN和潜在的其他Nrf2调节器对SARS-CoV-2的生理抗病毒功效至关重要.
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