Combinatory treatment of Covid-19 with remdesivir and the repurposed drugs fluoxetine and itraconazole

The antiviral potential of the antifungal itraconazole and the antidepressant fluoxetine was tested on the production of infectious SARS-CoV-2 particles in the polarized Calu-3 cell culture model and the added benefit of a combinatory use of these host-directed drugs with the direct acting antiviral remdesivir, an inhibitor of viral RNA polymerase was evaluated

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.

Although in these studies all the three drugs were dissolved in DMSO, the followers of the Cyclodextrin News blog know well that all of them can be solubilized by CDs. Itraconazole is marketed as an oral formulation solubilized by HPBCD (Sporanox) and remdesivir as an i.v. infusion solution formulated by SBECD (Veclury). Also the complexation of fluoxetine with CDs has been thoroughly studied in the past decades.

Sebastian Schloer, Linda Brunotte, Angeles Mecate-Zambrano, Shuyu Zheng, Jing Tang, Stephan Ludwig, Ursula Rescher (2021) Drug synergy of combinatory treatment with remdesivir and the repurposed drugs fluoxetine and itraconazole effectively impairs SARS-CoV-2 infection in vitro. British Journal of Pharmacology 178, 2339-2350. https://doi.org/10.1111/bph.15418(2021)