Despite successful vaccination programs, effective and readily available drugs for treating COVID-19 are still needed. Currently, both anti-inflammatory and antiviral treatment options are used, but with only limited success. The immunophilin inhibitor cyclosporin A (CsA) combines antiviral and immunomodulatory effects and is a promising candidate for COVID-19 treatment. CsA is an immunosuppressive drug that is used, among other applications, to prevent graft-versus-host disease after organ transplantation. In addition, CsA was found to block replication of different viruses in vitro, including SARS-CoV-2.
In a German Center of Lung Research (DZL) collaboration with the group of Prof. Herold (University of Gießen), Fraunhofer researchers demonstrated strong antiviral potency of CsA against different SARS-CoV-2 isolates in translational in-vitro, ex-vivo and in-vivo models (Sauerhering et al., 2022: DOI 10.1164/rccm.202108-1830LE). The researchers investigated the antiviral and anti-inflammatory efficacy of this drug in human precision-cut lung slices (PCLSs) – evidence of efficient SARS-CoV-2 replication in PCLS had previously been provided. Treatment with CsA significantly reduced virus titers in the medium and E gene RNA, restored vitality of PCLS, and decreased proinflammatory cytokine concentrations in supernatant of infected PCLS. These results may open the path for inhalation treatment of COVID-19 patients using adjusted CsA formulations – with high local efficacy but low systemic side effects.