PDF(Pubmed)
Abstract：
Viral infection treatment is a difficult task due to its complex structure and metabolism. Additionally, viruses can alter the metabolism of host cells, mutate, and readily adjust to harsh environments. Coronavirus stimulates glycolysis, weakens mitochondrial activity, and impairs infected cells. In this study, we investigated the efficacy of 2-DG in inhibiting coronavirus-induced metabolic processes and antiviral host defense systems, which have not been explored so far. 2-Deoxy-d-glucose (2-DG), a molecule restricting substrate availability, has recently gained attention as a potential antiviral drug. The results revealed that 229E human coronavirus promoted glycolysis, producing a significant increase in the concentration of fluorescent 2-NBDG, a glucose analog, particularly in the infected host cells. The addition of 2-DG decreased its viral replication and suppressed infection-induced cell death and cytopathic effects, thereby improving the antiviral host defense response. It was also observed that administration of low doses of 2-DG inhibited glucose uptake, indicating that 2-DG consumption in virus-infected host cells was mediated by high-affinity glucose transporters, whose levels were amplified upon coronavirus infection. Our findings indicated that 2-DG could be a potential drug to improve the host defense system in coronavirus-infected cells.
摘要：
由于其复杂的结构和代谢，病毒感染的治疗是一项艰巨的任务。此外,病毒可以改变宿主细胞的新陈代谢，变异，并易于适应恶劣的环境。冠状病毒刺激糖酵解，削弱线粒体活性，并损害受感染的细胞。在这项研究中,我们研究了2-DG在抑制冠状病毒诱导的代谢过程和抗病毒宿主防御系统中的功效，到目前为止还没有被探索过。2-脱氧-d-葡萄糖（2-DG），一种限制底物可用性的分子，最近作为一种潜在的抗病毒药物引起了人们的注意。结果显示，229E人冠状病毒促进糖酵解，产生荧光2-NBDG浓度的显着增加，葡萄糖类似物，特别是在受感染的宿主细胞中。添加2-DG减少其病毒复制并抑制感染诱导的细胞死亡和细胞病变效应。从而提高抗病毒宿主的防御反应。还观察到低剂量的2-DG的给药抑制葡萄糖摄取,表明病毒感染的宿主细胞中的2-DG消耗是由高亲和力葡萄糖转运蛋白介导的，其水平在冠状病毒感染后被放大。我们的发现表明，2-DG可能是改善冠状病毒感染细胞中宿主防御系统的潜在药物。
