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

Show full item record



Permalink

http://hdl.handle.net/10138/335997

Citation

Brunotte , L , Zheng , S , Mecate-Zambrano , A , Tang , J , Ludwig , S , Rescher , U & Schloer , S 2021 , ' Combination Therapy with Fluoxetine and the Nucleoside Analog GS-441524 Exerts Synergistic Antiviral Effects against Different SARS-CoV-2 Variants In Vitro ' , Pharmaceutics , vol. 13 , no. 9 , 1400 . https://doi.org/10.3390/pharmaceutics13091400

Title: Combination Therapy with Fluoxetine and the Nucleoside Analog GS-441524 Exerts Synergistic Antiviral Effects against Different SARS-CoV-2 Variants In Vitro
Author: Brunotte, Linda; Zheng, Shuyu; Mecate-Zambrano, Angeles; Tang, Jing; Ludwig, Stephan; Rescher, Ursula; Schloer, Sebastian
Contributor organization: Research Program in Systems Oncology
Faculty of Medicine
Date: 2021-09-03
Language: eng
Number of pages: 13
Belongs to series: Pharmaceutics
ISSN: 1999-4923
DOI: https://doi.org/10.3390/pharmaceutics13091400
URI: http://hdl.handle.net/10138/335997
Abstract: 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.
Subject: EBOLA
FUNCTIONAL INHIBITORS
GS-5734
HOST-DIRECTED THERAPIES
MORTALITY
PRODRUG
SARS-CoV-2
VIRUS
combination therapy
fluoxetine
nucleoside GS-441524
synergy
317 Pharmacy
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


Files in this item

Total number of downloads: Loading...

Files Size Format View
pharmaceutics_13_01400_2_.pdf 1.692Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record