综合的表型查和化学蛋白质组学识别了调节病毒翻译和复制的ETF1配体
Arthur S Kim1,2, Kevin Ma2, Christopher J Reinhardt1
1Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037.
概括
通过准真核转化终结因子1 (ETF1) 来抑制SARS-CoV-2复制的新型照片立体探针被确定. 这些分子通过调节宿主翻译过程,提供了一种新的广泛的抗病毒策略.
科学领域:
- 病毒学 病毒学
- 药物发现 药物发现 药物发现
- 分子生物学分子生物学
背景情况:
- 像SARS-CoV-2这样的新兴病毒对全球健康构成风险.
- 现有的抗病毒药物因耐药性而面临挑战.
- 迫切需要新的广泛的抗病毒策略.
研究的目的:
- 识别具有广泛抗病毒活性的新型小分子.
- 研究这些分子的作用机制和点.
- 探索ETF1作为潜在的抗病毒药物点.
主要方法:
- 对光反应小分子的表型选.
- 结构-活性关系研究和化学蛋白质组学.
- 采用纯化的ETF1和病毒复制研究的体外测定.
主要成果:
- 确定了抑制SARS-CoV-2复制的照片立体探针.
- 确定真核转化终结因子1 (ETF1) 作为分子标.
- 证明照片立体探头可以调节编程的核糖体移,而不会降解ETF1.
- 对使用非正规的核糖体框架转移的其他病毒显示出有效性.
结论:
- 照片立体探测器代表了一类机械上不同的ETF1配体.
- 宿主翻译终止是抗病毒药物开发的可行目标.
- 这些发现为广泛的抗病毒疗法开辟了新的途径.
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