Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA.
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA.
Biochem Biophys Res Commun. 2024 Nov 19;734:150763. doi: 10.1016/j.bbrc.2024.150763. Epub 2024 Sep 28.
While vaccines were being developed, the SARS-CoV-2 pandemic triggered a race to find known drugs that could be quickly repurposed to treat patients. One such candidate was famotidine, which retrospective cohort studies had shown increased survival in hospitalized patients. Computational studies had suggested that famotidine may target early viral proteases; however, ultimately, famotidine was shown not to function as a viral inhibitor. In contrast, we have observed a change in the cellular levels of phospho-tyrosine in A549 lung epithelial cells following treatment with famotidine. This quick change in phosphorylation was due mainly to a dose-dependent increase in cellular production of HO. Notably, these changes in phospho-tyrosine levels were able to affect cell signaling; we detected an increased short- and long-term response to IFNα stimulation. Our results suggest that famotidine can increase the anti-viral state of non-infected cells thereby potentially increasing viral resistance.
在疫苗研发的同时，SARS-CoV-2 大流行引发了一场寻找已知药物的竞赛，这些药物可以被快速重新用于治疗患者。法莫替丁就是这样一种候选药物，回顾性队列研究表明，住院患者的生存率有所提高。计算研究表明，法莫替丁可能靶向早期病毒蛋白酶；然而，最终，法莫替丁并没有表现出作为病毒抑制剂的功能。相比之下，我们观察到法莫替丁处理后 A549 肺上皮细胞中磷酸酪氨酸的细胞水平发生了变化。这种磷酸化的快速变化主要是由于细胞中 HO 的产生呈剂量依赖性增加。值得注意的是，这些磷酸酪氨酸水平的变化能够影响细胞信号转导；我们检测到 IFNα 刺激的短期和长期反应增加。我们的结果表明，法莫替丁可以增加未感染细胞的抗病毒状态，从而可能增加病毒耐药性。
