Poschet Jens F, Perkett Elizabeth A, Timmins Graham S, Deretic Vojo
Departments of Molecular Genetics and Microbiology, University of New Mexico Health Science Center.
Departments of Pediatrics, University of New Mexico Health Science Center.
bioRxiv. 2020 Mar 31:2020.03.29.008631. doi: 10.1101/2020.03.29.008631.
There is interest in the use of chloroquine/hydroxychloroquine (CQ/HCQ) and azithromycin (AZT) in COVID-19 therapy. Employing cystic fibrosis respiratory epithelial cells, here we show that drugs AZT and ciprofloxacin (CPX) act as acidotropic lipophilic weak bases and confer in vitro effects on intracellular organelles similar to the effects of CQ. These seemingly disparate FDA-approved antimicrobials display a common property of modulating pH of endosomes and trans-Golgi network. We believe this may in part help understand the potentially beneficial effects of CQ/HCQ and AZT in COVID-19, and that the present considerations of HCQ and AZT for clinical trials should be extended to CPX.
人们对使用氯喹/羟氯喹(CQ/HCQ)和阿奇霉素(AZT)治疗新冠肺炎感兴趣。在此,我们利用囊性纤维化呼吸道上皮细胞表明,药物AZT和环丙沙星(CPX)作为亲酸性亲脂性弱碱,对细胞内细胞器产生的体外效应与CQ的效应相似。这些看似不同但已获美国食品药品监督管理局批准的抗菌药物具有调节内体和反式高尔基体网络pH值的共同特性。我们认为,这可能在一定程度上有助于理解CQ/HCQ和AZT在新冠肺炎治疗中潜在的有益作用,并且目前对HCQ和AZT用于临床试验的考量应扩展至CPX。