多巴胺及其前体莱沃多巴通过形成一种蛋白质来使SARS-CoV-2主要蛋白酶失活
Meng Hao1, Yufeng He1, Tingting Song1
1State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Institute of Health and Medicine, Hefei Comprehensive National Science Center, Anhui Agricultural University, Hefei, 230036, China.
Free radical biology & medicine
|May 8, 2024
概括
多巴胺和莱沃多巴通过向病毒Mpro酶来抑制SARS-CoV-2的复制. 这表明通过吸入输送的利沃多巴可能是潜在的COVID-19治疗方法.
科学领域:
- 神经科学是一个神经科学.
- 病毒学 病毒学
- 药理学 药理学是指药理学的学科.
背景情况:
- 尽管存在ACE2受体,SARS-CoV-2RNA/抗原在大脑中通常不存在或很低,这表明神经细胞中发生了流产性感染.
- 内源性多巴胺和勒沃多巴存在于大脑中的微分子到毫米分子度.
研究的目的:
- 研究多巴胺和莱沃多巴对SARS-CoV-2主要蛋白酶 (Mpro) 的抑制作用.
- 探索CVT-301 (吸入式乐伏多巴) 作为针对肺部Mpro的COVID-19治疗药物的潜力.
主要方法:
- 评估了多巴胺和莱沃多巴在体外抑制SARS-CoV-2 Mpro活性.
- 使用硫醇检测和LC-MS/MS来识别Mpro-氨酸添加物.
- 审查了关于肺部药物输送和CVT-301.1的现有文献.
主要成果:
- 多巴胺和乐伏多巴剂量和时间依赖,通过形成蛋白质来抑制SARS-CoV-2 Mpro活性.
- 经LC-MS/MS证实了多巴胺或levodopa-o-quinone对Mpro.的活性位点Cys145-SH的共价结合.
- 利沃多巴显示Mpro抑制作用略强于多巴胺.
结论:
- 这些发现解释了由于内源Mpro抑制导致神经细胞中SARS-CoV-2复制效率低下的原因.
- 吸入式勒沃多巴 (CVT-301) 值得紧急调查,因为它是针对肺部的Mpro抑制剂,用于COVID-19治疗.
关键词:
在 COVID-19 疫情中,多巴胺是一种多巴胺.利沃多帕 (Levodopa) 是一种可靠的药物.这是SARS-CoV-2的主要蛋白酶.蛋白质是一种蛋白质.醇 (Thiol) 是一种类型的醇.更多相关视频
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