通过抑制perfringolysin O,重新将拉贝普拉酸作为一种抗Clostridium perfringens药物
Guizhen Wang1,2,3, Yan Liu1, Le Deng1
1State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130012, China.
Journal of applied microbiology
|November 29, 2023
概括
拉贝普拉酸有效地抑制了从Clostridium perfringens中产生的毒素青素O (PFO),一种毒素. 这种候选药物显示出治疗感染和改善家禽料安全的潜力.
科学领域:
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
- 食品安全 食品安全
背景情况:
- 杆菌感染对食品安全,人类健康和家禽产业构成风险.
- 抗病毒策略为开发新抗微生物药物提供了替代方法.
- 黄素O (PFO) 是一个关键的C. perfringens外毒素,也是治疗干预的有希望的目标.
研究的目的:
- 从现有的药物库中识别出对perfringolysin O (PFO) 的抑制剂.
- 评估已识别的化合物对C. perfringens的抗病毒性潜力.
主要方法:
- 对FDA批准的药物库进行基于活动的查,以识别PFO抑制剂.
- 拉贝普拉 (RS) 抑制PFO的体外分析,包括IC50的确定.
- 分子对接和H键分析以阐明RS和PFO之间的相互作用.
- 在Galleria mellonella感染模型中进行RS的体内疗效测试.
主要成果:
- 确定了六种PFO抑制剂,其中拉贝普拉 (RS) 显示出最强的抑制作用 (IC50 = 1.82 ± 0.746 μg/mL).
- RS与PFO中的特定氨基酸残留物结合,阻止其寡合化和随后的细胞毒性.
- 在PFO感染的Galleria mellonella中,RS治疗显著提高了生存率,并减少了病理损伤.
结论:
- 拉贝普拉通过向PFO.表现出对C. perfringens显著的抗病毒活性.
- RS是开发针对C. perfringens感染的新疗法的潜在候选药物.
- 这项研究突出了FDA批准的药物用于抗击细菌感染的治疗潜力.
相关概念视频
Drugs for Treatment of Constipation-Predominant IBS
179
Pharmacological therapies for IBS-C are designed to alleviate abdominal discomfort and enhance bowel function. In patients with IBS-C, fiber supplements may help soften stools and decrease straining, but may also lead to increased gas production and bloating. Osmotic laxatives like milk of magnesia are frequently used to soften stools and increase stool frequency in IBS-C patients. In addition, two drugs approved for use in severe IBS-C adult cases are linaclotide (Linzess) and lubiprostone...
179
Acid Suppressive Drugs for Peptic Ulcer Disease: Proton Pump Inhibitors
435
Peptic ulcers, often induced by H. pylori infections or NSAID usage, arise from disruptions in the delicate balance of gastric acid production. Peptic ulcers stem from heightened gastric acid levels due to H. pylori infections or NSAID use. The protective mucus layer diminishes in the presence of these factors, allowing gastric acid to erode the stomach lining and form ulcers.
Gastric acid, a potent cocktail of hydrogen and chloride ions, is produced in specialized parietal cells within the...
Gastric acid, a potent cocktail of hydrogen and chloride ions, is produced in specialized parietal cells within the...
435
Drugs for Peptic Ulcer Disease: Sucralfate as Mucosal Protective Agents
499
In the intricate landscape of the gastric lumen, excessive acid secretion disrupts the natural defense mechanisms, weakening the mucus-bicarbonate barrier. This vulnerability allows pepsin to infiltrate epithelial cells, digesting mucosal proteins and triggering erosion, leading to ulcer formation.
In this scenario, mucosal protective agents like sucralfate play an essential role. Sucralfate, a complex of sulfated sucrose and aluminum hydroxide, demonstrates its usefulness in acidic conditions,...
In this scenario, mucosal protective agents like sucralfate play an essential role. Sucralfate, a complex of sulfated sucrose and aluminum hydroxide, demonstrates its usefulness in acidic conditions,...
499
Combined Effects of Drugs: Synergism
3.9K
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
3.9K


