寨卡病毒干循环A中的高分辨率RNA三级结构用于开发抑制性小分子
Jerricho Tipo1, Keerthi Gottipati2,3, Kyung H Choi4,3
1Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, Texas 77555, USA.
概括
研究人员确定了寨卡病毒干环A的结构,揭示了单核酸突起如何提供灵活性. 这一发现有助于开发针对病毒RNA合成的小分子抑制剂.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 药用化学 医学化学
背景情况:
- 病毒,包括寨卡病毒 (ZIKV) 和登革热病毒 (DENV),是人类重要的病原体.
- 在ZIKV和DENV基因组中,有一个5'干环A (SLA),这对病毒RNA复制和NS5聚合酶的甲基化至关重要.
- ZIKV和DENV SLAs的定义折叠为小分子抑制剂提供了潜在的结合点.
研究的目的:
- 阐明ZIKV SLA用于向药物发现的结构基础.
- 为了确定可以抑制ZIKV SLA促进器功能的小分子.
主要方法:
- 确定ZIKV SLA.的底部和顶部茎的高分辨率晶体结构.
- 在单个U或G突起中分析核酸构造.
- 对结合ZIKV SLA茎的化合物进行选.
主要成果:
- 在ZIKV SLA结构中揭示了膨胀核酸 (U或G) 的多重方向.
- 通过堆叠或基础三重相互作用,证明了膨胀形状的稳定.
- 识别了与ZIKV SLA.的底部和顶部茎结合的化合物.
结论:
- 像ZIKV SLA这样的RNA结构中的单个未配对核酸赋予了灵活性.
- 这些柔性区域的形状受周围的化学环境的影响.
- 已识别的ZIKV SLA结合化合物是抗病毒药物开发的有希望的线索.
相关概念视频
siRNA - Small Interfering RNAs
16.8K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
16.8K
RNA Interference
26.0K
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
26.0K
Experimental RNAi
6.1K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.1K
RNA Structure
4.8K
The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
4.8K


