发现了针对SARS-CoV-2病毒基因组中的框架转移元素RNA的小分子
Mo Yang1, Feyisola P Olatunji1, Curran Rhodes1
1Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702-1201, United States.
ACS medicinal chemistry letters
|June 14, 2023
概括
研究人员发现了新的小分子,针对SARS-CoV-2框架转移元素 (FSE) RNA. 这些化合物显示出通过抑制病毒蛋白表达来控制病毒复制的潜力.
科学领域:
- 病毒学 病毒学
- 药用化学 医学化学
- 在RNA生物学,RNA生物学.
背景情况:
- 针对SARS-CoV-2中的结构RNA元素提供了一个有希望的抗病毒策略.
- 可以开发出小分子,通过与特定的RNA结构相互作用来抑制病毒复制.
研究的目的:
- 发现和描述针对SARS-CoV-2框架转移元素 (FSE) 的新型小分子.
- 评估这些新型化合物的抗病毒活性.
主要方法:
- 使用高通量小分子微阵列 (SMM) 查来识别潜在的结合剂.
- 合成和结构-活性关系 (SAR) 研究针对一种新的类型的氨基基纳林配体进行.
- 用于表征,使用了正角生物物理测试.
- 进行了体外双光酶和细胞内双光报告器框架转移试验,以评估活性.
主要成果:
- 确定了一种针对SARS-CoV-2 FSE的新一类氨基基纳素配体.
- 这些化合物对FSERNA具有中微分子结合亲和力 (KD = 60 ± 6 μM).
- 与已知的FSE结合剂相比,提出了一个不同的结合模式.
- 化合物在体外和细胞内框架转移试验中都表现出活性.
结论:
- 已识别的氨基基纳素化合物代表了一类新的SARS-CoV-2 FSE结合剂.
- 这些分子通过调节病毒蛋白质表达,显示出开发抗病毒疗法的潜力.
- 用类似药物的化合物向结构化RNA元素是抗病毒药物发现的可行策略.
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