期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 178, 期 11, 页码 2339-2350出版社
WILEY
DOI: 10.1111/bph.15418
关键词
combination therapy; drug repurposing; fluoxetine; itraconazole; remdesivir; SARS‐ CoV‐ 2
资金
- Academy of Finland [317680]
- German Research Foundation (DFG)
- European Research Council [716063]
- Innovative Medizinische Forschung (IMF) of the Munster Medical School [SC121912]
- Interdisciplinary Center for Clinical Research Muenster (IZKF) [Re2/022/20]
- CRC 1348 Dynamic Cellular Interfaces [A10]
- CRC1009 Breaking Barriers [A6, B02, Lu477/23-1]
The combination of itraconazole-remdesivir and fluoxetine-remdesivir effectively inhibits the production of infectious SARS-CoV-2 particles with synergistic effects, showing promising therapeutic options for controlling COVID-19.
Background and Purpose The SARS-COV-2 pandemic and the global spread of coronavirus disease 2019 (COVID-19) urgently call for efficient and safe antiviral treatment strategies. A straightforward approach to speed up drug development at lower costs is drug repurposing. Here, we investigated the therapeutic potential of targeting the interface of SARS CoV-2 with the host via repurposing of clinically licensed drugs and evaluated their use in combinatory treatments with virus- and host-directed drugs in vitro. Experimental Approach We tested the antiviral potential of the antifungal itraconazole and the antidepressant fluoxetine on the production of infectious SARS-CoV-2 particles in the polarized Calu-3 cell culture model and evaluated the added benefit of a combinatory use of these host-directed drugs with the direct acting antiviral remdesivir, an inhibitor of viral RNA polymerase. Key Results Drug treatments were well-tolerated and potently impaired viral replication. Importantly, both itraconazole-remdesivir and fluoxetine-remdesivir combinations inhibited the production of infectious SARS-CoV-2 particles > 90% and displayed synergistic effects, as determined in commonly used reference models for drug interaction. Conclusion and Implications Itraconazole-remdesivir and fluoxetine-remdesivir combinations are promising starting points for therapeutic options to control SARS-CoV-2 infection and severe progression of COVID-19.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据