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bioRxiv · 10.1101/2020.10.16.342410

Drug synergy of combinatory treatment with remdesivir and the repurposed drugs fluoxetine and itraconazole effectively impairs SARS-CoV-2 infection in vitro

Rescher, U.·Schloer, S.·Brunotte, L.·Mecate-Zambrano, A.·Zheng, S.·Tang, J.·Ludwig, S.
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Abstract

The SARS-COV-2 pandemic and the global spread of coronavirus disease 2019 (COVID-19) urgently calls 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 host- SARS-CoV-2 interface via repurposing of clinically licensed drugs and evaluated their use in combinatory treatments with virus- and host-directed drugs. We tested the antiviral potential of repurposing 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 remdesivir, an inhibitor of viral RNA polymerase. Drug treatments were well-tolerated and potent impaired viral replication was observed with all drug treatments. Importantly, both itraconazole-remdesivir and fluoxetine-remdesivir combinations inhibited the production of infectious SARS-CoV-2 particles > 90% and displayed synergistic effects in commonly used reference models for drug interaction. Itraconazole-Remdesivir and Fluoxetine-Remdesivir combinations are promising therapeutic options to control SARS-CoV-2 infection and severe progression of COVID-19.

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Rescher, U., Schloer, S., Brunotte, L., Mecate-Zambrano, A., Zheng, S., Tang, J., Ludwig, S.. 2020-10-16. Drug synergy of combinatory treatment with remdesivir and the repurposed drugs fluoxetine and itraconazole effectively impairs SARS-CoV-2 infection in vitro. https://doi.org/10.1101/2020.10.16.342410

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