用Bis-thiourea化合物准G-Quadruplex可以抑制SARS-CoV-2复制的发生
Shogo Sasaki1, Shogo Nakajima2, Rena Nohara1
1Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei , Tokyo184-8588, Japan.
ACS infectious diseases
|July 17, 2025
概括
研究人员在SARS-CoV-2中确定了一个独特的G-四重复 (G4) RNA结构. 针对这种G4动机的新型双尿素化合物显示出对病毒的显著抗病毒活性,提供了一种新的治疗策略.
科学领域:
- 病毒学 病毒学
- 药用化学 医学化学
- 分子生物学分子生物学
背景情况:
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 持续发生突变,需要新的治疗点.
- 由于它们在抑制病毒复制中的作用,G四倍体 (G4s) 是抗病毒药物开发的有希望的标.
研究的目的:
- 在SARS-CoV-2基因组中识别G-四重复结构.
- 发现选择性地与这些病毒G4结构结合的小分子,以潜在的治疗用途.
主要方法:
- 利用G4预测工具在SARS-CoV-2RNA中识别出一种独特的G4形成序列 (SC-2).
- 采用醇色 (TO) 位移试验来选G4结合剂的内部化合物库.
- 进行了基于细胞的测定 (VeroE6 / TMPRSS2) 来评估抗病毒活性和病毒RNA水平.
主要成果:
- 在SARS-CoV-2基因组中确定了一个独特的SC-2 G4基因.
- 发现了与SC-2 G4动机结合的bis-urea/bis-thiourea化合物.
- 一种特定的双尿素化合物 (BT1) 显示出强大的SARS-CoV-2复制抑制,与remdesivir可比,并降低了病毒RNA水平.
结论:
- 针对SC-2 G4基因的双尿素化合物代表了开发抗SARS-CoV-2药物的有希望的新策略.
- 该研究验证了G4结构作为针对SARS-CoV-2的可行的治疗点.
- 光标记的化合物在复制过程中显示在双链RNA附近的积累,这表明病毒RNAG4s的有效向.
相关概念视频
Inhibitors of Bacterial Protein Synthesis
Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
Inhibitors of Bacterial DNA Synthesis
Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
Inhibitors of Viral Protein Synthesis
Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Antiviral Nucleoside Inhibitors
Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...


