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Article

Combination Therapy with Fluoxetine and the Nucleoside Analog GS-441524 Exerts Synergistic Antiviral Effects against Different SARS-CoV-2 Variants In Vitro

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Institute of Virology, Center for Molecular Biology of Inflammation, and “Cells in Motion” Interfaculty Centre, University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany
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Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8, 00029 Helsinki, Finland
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Institut-Associated Research Group Regulatory Mechanisms of Inflammation, Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, and “Cells in Motion” Interfaculty Centre, University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Lucreția Udrescu, Ludovic Kurunczi, Paul Bogdan and Mihai Udrescu
Pharmaceutics 2021, 13(9), 1400; https://doi.org/10.3390/pharmaceutics13091400
Received: 20 July 2021 / Revised: 30 August 2021 / Accepted: 1 September 2021 / Published: 3 September 2021
(This article belongs to the Special Issue In Silico Strategies for Prospective Drug Repositionings)
The ongoing SARS-CoV-2 pandemic requires efficient and safe antiviral treatment strategies. Drug repurposing represents a fast and low-cost approach to the development of new medical treatment options. The direct antiviral agent remdesivir has been reported to exert antiviral activity against SARS-CoV-2. Whereas remdesivir only has a very short half-life time and a bioactivation, which relies on pro-drug activating enzymes, its plasma metabolite GS-441524 can be activated through various kinases including the adenosine kinase (ADK) that is moderately expressed in all tissues. The pharmacokinetics of GS-441524 argue for a suitable antiviral drug that can be given to patients with COVID-19. Here, we analyzed the antiviral property of a combined treatment with the remdesivir metabolite GS-441524 and the antidepressant fluoxetine in a polarized Calu-3 cell culture model against SARS-CoV-2. The combined treatment with GS-441524 and fluoxetine were well-tolerated and displayed synergistic antiviral effects against three circulating SARS-CoV-2 variants in vitro in the commonly used reference models for drug interaction. Thus, combinatory treatment with the virus-targeting GS-441524 and the host-directed drug fluoxetine might offer a suitable therapeutic treatment option for SARS-CoV-2 infections. View Full-Text
Keywords: combination therapy; SARS-CoV-2; nucleoside GS-441524; fluoxetine; synergy combination therapy; SARS-CoV-2; nucleoside GS-441524; fluoxetine; synergy
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MDPI and ACS Style

Brunotte, L.; Zheng, S.; Mecate-Zambrano, A.; Tang, J.; Ludwig, S.; Rescher, U.; Schloer, S. Combination Therapy with Fluoxetine and the Nucleoside Analog GS-441524 Exerts Synergistic Antiviral Effects against Different SARS-CoV-2 Variants In Vitro. Pharmaceutics 2021, 13, 1400. https://doi.org/10.3390/pharmaceutics13091400

AMA Style

Brunotte L, Zheng S, Mecate-Zambrano A, Tang J, Ludwig S, Rescher U, Schloer S. Combination Therapy with Fluoxetine and the Nucleoside Analog GS-441524 Exerts Synergistic Antiviral Effects against Different SARS-CoV-2 Variants In Vitro. Pharmaceutics. 2021; 13(9):1400. https://doi.org/10.3390/pharmaceutics13091400

Chicago/Turabian Style

Brunotte, Linda, Shuyu Zheng, Angeles Mecate-Zambrano, Jing Tang, Stephan Ludwig, Ursula Rescher, and Sebastian Schloer. 2021. "Combination Therapy with Fluoxetine and the Nucleoside Analog GS-441524 Exerts Synergistic Antiviral Effects against Different SARS-CoV-2 Variants In Vitro" Pharmaceutics 13, no. 9: 1400. https://doi.org/10.3390/pharmaceutics13091400

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