通过向宿主蛋白质eEF1A,plitidepsin对SARS-CoV-2具有强大的临床前疗效
Kris M White1,2, Romel Rosales3,2, Soner Yildiz3,2
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. kris.white@mssm.edu nevan.krogan@ucsf.edu adolfo.garcia-sastre@mssm.edu.
Science (New York, N.Y.)
|January 26, 2021
概括
在实验室中,plitidepsin对SARS-CoV-2具有强大的抗病毒活性,显著超过remdesivir. 这种针对真核转换延长因子1A的药物有效地减少了小鼠模型中的病毒复制,这表明它对COVID-19治疗具有前景.
科学领域:
- 病毒学
- 药理学
- 分子生物学
背景情况:
- 严重急性呼吸系统冠状病毒2 (SARS-CoV-2) 与宿主转化机器相互作用.
- 翻译抑制剂对SARS-CoV-2具有强大的抗病毒作用.
研究的目的:
- 评估普利蒂素对SARS-CoV-2的抗病毒活性.
- 调查化在COVID-19治疗中的作用机制和体内疗效.
主要方法:
- 在体外抗病毒试验中比较普利蒂素和雷梅西维尔.
- 药物耐药性突变分析以确定药物目标.
- 在SARS-CoV-2感染的小鼠模型中进行体内疗效研究.
主要成果:
- 与雷梅西维尔相比,plitidepsin 在体外显示出显著更高的抗病毒功效 (90% 抑制度= 0. 88 nM).
- 通过抑制真核转化延长因子1A (eEF1A) 来介导抗病毒活性.
- 在小鼠肺部,预防性普利素治疗使病毒复制减少了两倍.
结论:
- 普利提德是体外对抗SARS-CoV-2的强效抗病毒药物.
- 药物的有效性与eEF1A抑制有关.
- 普利提德作为COVID-19治疗候选药物具有前景.
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