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塞法兰丁通过破坏Hsp90-Cdc37复合体来抑制AKT相关途径,从而抑制非洲猪瘟病毒的复制

Guanming Su¹, Lizhan Su², Ding Luo²

¹Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Laboratory Animal Center, Guangdong Medical University, Dongguan 523808, China.

International journal of biological macromolecules

|November 1, 2024

概括

塞法兰丁 (CEP) 通过破坏Hsp90-Cdc37复合体来抑制非洲猪瘟病毒 (ASFV) 复制,减少AKT酸化,糖解和炎症. 这为ASFV感染提供了潜在的新治疗策略.

科学领域:

病毒学和免疫学病毒学和免疫学
药物发现和开发药物发现和开发

背景情况:

非洲猪瘟 (ASF) 是全球主要的猪业威胁,目前还没有疫苗或治疗方法.
日本批准的天然化物塞法兰 (CEP) 已显示出对ASFV的初步抗病毒活性.

研究的目的:

阐明塞法兰 (CEP) 抑制非洲猪瘟病毒 (ASFV) 复制的分子机制.
为了确定ASFV感染的新型治疗点.

主要方法:

研究了ASFV,Hsp90,Cdc37和AKT信号通路之间的相互作用.
评估了CEP对Hsp90-Cdc37复合体,AKT酸化,糖解和炎症性细胞因子产生的影响.
评估了乳酸和IL-1β对ASFV复制的影响.

主要成果:

ASFV感染增加了Hsp90-Cdc37复合体的形成和AKT酸化,促进病毒复制.
CEP破坏了Hsp90-Cdc37复合体,减少了p-AKT,糖解,乳酸生产和NF-κB介导的IL-1β表达.
增加的乳酸和IL-1β协同增强ASFV复制;CEP减轻了这些影响.

结论:

通过向Hsp90-Cdc37-AKT/糖解/NF-κB轴,CEP有效地抑制ASFV的复制.
Hsp90-Cdc37复合体和糖解被确定为ASFV的新型抗病毒标.
对猪进行进一步的体内研究至关重要,以评估CEP对ASF的治疗潜力.

关键词:

在 AKT AKT 里面.非洲猪瘟病毒 (ASFV) 病毒塞法兰丁 (CEP) 是一种葡萄糖溶解是什么? 葡萄糖溶解在Hsp90-Cdc37复合体中.在 NF-κBB 中.

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