Antifungal

Coronavirus

2019-20 coronavirus outbreak

Ecology

Biology

Viral replication

Virology

Receptor

Dermatology

Fluoxetine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Outbreak

Drug

Antiviral drug

Coronavirus disease 2019 (COVID-19)

Genetics

Repurposing

In vitro

Infectious disease (medical specialty)

Internal medicine

Pharmacology

Drug repositioning

Medicine

Itraconazole

Virus

Disease

Serotonin

British Journal of Pharmacology

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.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.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.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.

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