西克洛皮洛克斯通过向铁代谢来抑制波克斯病毒的复制
Anil Pant1, Djamal Brahim Belhaouari1, Lara Dsouza1
1Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, USA.
bioRxiv : the preprint server for biology
|August 8, 2025
概括
一种抗真菌药物Ciclopirox (CPX) 通过结合铁,有效抑制疫苗病毒 (VACV) 复制. 这种重新设计的药物显示出作为一种广泛的抗病毒药物,可以对抗像水病毒这样的orthopoxvirus.
科学领域:
- 病毒学 病毒学
- 传染性疾病 传染性疾病
- 药物发现 药物发现 药物发现
背景情况:
- 脊髓灰质炎病毒对全球健康构成重大威胁,推动了对新的抗病毒疗法的需求.
- 高通量查确定了 FDA 批准的抗真菌药物 ciclopirox (CPX) 作为疫苗病毒 (VACV) 复制的潜在抑制剂.
研究的目的:
- 描述环皮洛克斯 (CPX) 抗病毒活性和抗毒病毒作用机制.
- 评估CPX作为一种潜在的广泛抗病毒药物,用于治疗脊髓炎病毒感染.
主要方法:
- 人类初级纤维细胞被用来评估CPX的抗病毒疗效和细胞毒性.
- 进行了涉及铁补充和铁依赖酶过度表达的救援实验.
- 对牛病毒,病毒和ex vivo小鼠肺组织进行了抗病毒活性测试.
主要成果:
- CPX在低EC50和高CC50值下显著抑制了VACV复制,表明了良好的安全性.
- 主要的作用机制涉及细胞内铁 (Fe3+和Fe2+) 的化.
- 在实验室中,CPX有效地抑制了牛和病毒的复制,并在老鼠肺组织中有效抑制了VACV.
结论:
- 主体的铁代谢对于小病毒的复制至关重要.
- 赛克洛皮洛克斯 (CPX) 是一个强大的阻断器的orthopoxvirus复制,通过铁化作用.
- CPX 是一个有前途的候选人,可以作为一种广泛的抗病毒药物来对抗天花病毒,包括天花病毒.
相关概念视频
Drug Metabolism: Phase I Reactions
3.6K
A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
3.6K
Oxidation of Phenols to Quinones
3.5K
In the presence of oxidizing agents, phenols are oxidized to quinones. Quinones can be easily reduced back to phenols using mild reducing agents. The electron-donating hydroxyl group enhances the reactivity of the aromatic ring, enabling oxidation of the ring even in the absence of an α hydrogen.
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox...
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox...
3.5K
Necrosis
4.8K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.8K
Cancer Therapies
7.9K
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
7.9K
Hepatic Drug Excretion: Enterohepatic Cycling
1.8K
Enterohepatic cycling involves the active secretion of drugs and their metabolites into the bile via transporters in the canalicular membrane of hepatocytes. This secretion is an integral part of the digestive process, releasing these substances into the gastrointestinal (GI) tract.
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
1.8K
Peroxisomes
14.4K
Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
14.4K


