Mahdi Mohamed, Hermán Levente, Réthelyi János M, Bálint Bálint László
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem tér 1, 4032 Debrecen, Hungary.
Infectology Clinic, University of Debrecen Clinical Centre, Bartók Béla út 2-26, 4031 Debrecen, Hungary.
Int J Mol Sci. 2022 Mar 30;23(7):3812. doi: 10.3390/ijms23073812.
Mapping non-canonical cellular pathways affected by approved medications can accelerate drug repurposing efforts, which are crucial in situations with a global impact such as the COVID-19 pandemic. Fluoxetine and fluvoxamine are well-established and widely-used antidepressive agents that act as serotonin reuptake inhibitors (SSRI-s). Interestingly, these drugs have been reported earlier to act as lysosomotropic agents, inhibitors of acid sphingomyelinase in the lysosomes, and as ligands of sigma-1 receptors, mechanisms that might be used to fight severe outcomes of COVID-19. In certain cases, these drugs were administered for selected COVID-19 patients because of their antidepressive effects, while in other cases, clinical studies were performed to assess the effect of these drugs on treating COVID-19 patients. Clinical studies produced promising data that encourage the further investigation of fluoxetine and fluvoxamine regarding their use in COVID-19. In this review, we summarize experimental data and the results of the performed clinical studies. We also provide an overview of previous knowledge on the tissue distribution of these drugs and by integrating this information with the published experimental results, we highlight the real opportunity of using these drugs in our fight against COVID-19.
绘制受已批准药物影响的非经典细胞通路图谱可以加速药物再利用的研究工作，这在像新冠疫情这样具有全球影响的情况下至关重要。氟西汀和氟伏沙明是成熟且广泛使用的抗抑郁药物，作为5-羟色胺再摄取抑制剂（SSRI）发挥作用。有趣的是，这些药物早前被报道可作为溶酶体促渗剂、溶酶体中酸性鞘磷脂酶的抑制剂以及σ-1受体的配体，这些机制可能用于对抗新冠的严重后果。在某些情况下，这些药物因具有抗抑郁作用而被用于特定的新冠患者，而在其他情况下，则开展了临床研究以评估这些药物对治疗新冠患者的效果。临床研究产生了有前景的数据，鼓励进一步研究氟西汀和氟伏沙明在新冠治疗中的应用。在这篇综述中，我们总结了实验数据以及已开展的临床研究结果。我们还概述了关于这些药物组织分布的先前知识，并通过将这些信息与已发表的实验结果相结合，强调了使用这些药物对抗新冠的实际机会。
