Inhibition of SARS-CoV-2 Infection by the Cyclophilin Inhibitor Alisporivir (Debio 025)
Laurent Softic, Rozenn Brillet, François Berry, Nazim Ahnou, Quentin Nevers, Margot Morin‐Dewaele, Sabah Hamadat, Patrice Bruscella, Slim Fourati, Jean–Michel Pawlotsky, Abdelhakim Ahmed‐Belkacem
Abstract
Cyclophilins play a key role in the life cycle of coronaviruses. Alisporivir (Debio 025) is a nonimmunosuppressive analogue of cyclosporine with potent cyclophilin inhibition properties. Alisporivir reduced SARS-CoV-2 RNA production in a dose-dependent manner in Vero E6 cells, with a 50% effective concentration (EC 50 ) of 0.46 ± 0.04 μM. Alisporivir inhibited a postentry step of the SARS-CoV-2 life cycle. These results justify rapidly conducting a proof-of-concept phase 2 trial with alisporivir in patients with SARS-CoV-2 infection.
Topics & Concepts
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Coronavirus disease 2019 (COVID-19)VirologyCyclophilin A2019-20 coronavirus outbreakBiologyMedicineInternal medicineMolecular biologyDiseaseInfectious disease (medical specialty)OutbreakSignaling Pathways in DiseaseToxin Mechanisms and ImmunotoxinsPARP inhibition in cancer therapy