Am J Respir Crit Care Med
In the present study, we demonstrate that Cyclosporine A (CsA), an FDA-approved, well-characterized immunosuppressive drug, acts as a potent antiviral against different SARS-CoV-2 isolates (including variants of concern) in translational in vitro/ex vivo and in vivo models. CsA treatment of primary human bronchial epithelial cells and donor lung-derived, ex vivo cultured precision-cut lung slices (PCLS) infected with SARS-CoV2 significantly reduced virus titers and viral E gene expression in comparison to DMSO-treated control. Moreover, application of CsA recovered metabolic activity of SARS-CoV2-infected PCLS and decreased proinflammatory cytokines release. Oral application of CsA in a COVID-19 mouse model efficiently reduced amount of viral RNA in lung homogenates of infected mice, diminished cell infiltration in lung tissue and did not blunt antigen-specific T cell response, as recently identified in translational MERS-CoV infection models (Sauerhering et al, ERJ, 2020). Taking together, we demonstrated a significant anti-SARS-CoV2 effect of CsA in different human-relevant models and suggest CsA as a potent first-line therapy agent in COVID-19 patients.