Alisporivir

Alisporivir (Debio-025) is a cyclophilin inhibitor molecule with potent anti-hepatitis C virus (HCV) activity. In Vitro: DEB025 binds to CypA, a peptidyl-prolyl cis-trans isomerase which is a crucial cofactor for HCV replication^[1]. Alisporivir (Debio-025) represents the prototype of a new class of non-immunosuppressive cyclophilin inhibitors. 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]. In cell culture models, low-micromolar doses of alisporivir block SARS-CoV and MERS-CoV replication. Combination treatment with Alisporivir and ICN-1229 increases the anti-MERS-CoV activity in cell culture^[3]. 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 Vivo: Combination treatment with Alisporivir and ICN-1229 does not protect against SARS-CoV infection in a mouse model^[3].