Alisporivir (Debio-025) is an analogue of cyclosporine A and represents the prototype of a new class of non-immunosuppressive cyclophilin inhibitors. DEB025 binds to CypA, a peptidyl-prolyl cis-trans isomerase which is a crucial cofactor for HCV replication[1]. Alisporivir prevents HCV protein-mediated collapse of the respiration-driven mitochondrial membrane potential. Alisporivir prevents HCV protein-mediated mitochondrial dysfunction outside the context of apoptosis, calcium overload, production of ROS, dysfunction[2]. Alisporivir pretreatment stimulates antigen presentation by hepatoma target cells, leading to enhancement of antigen-specific CD8+ T cell activation by 40%. Alisporivir induces an increase of MHC-I and beta-2 microglobulin on the surface of several cell lines[4]. In cell culture models, low-micromolar doses of alisporivir block SARS-CoV and MERS-CoV replication. Combination treatment with alisporivir and ribavirin increases the anti-MERS-CoV activity in cell culture[3].

Combination treatment with alisporivir and ribavirin does not protect against SARS-CoV infection in a mouse model[3].