Alisporivir (DEB-025) (Synonyms: Debio-025; DEB-025)

Alisporivir (DEB-025; Debio-025) is a cyclophilin inhibitor molecule with potent anti-hepatitis C virus (HCV) activity.

DEB025 binds to CypA, a peptidyl-prolyl cis-trans isomerase which is a crucial cofactor for HCV replication[1]. Alisporivir (Debio-025) is an analogue of cyclosporine A and 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 ribavirin 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].

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

[1]. Coelmont L, et al. DEB025 (Alisporivir) inhibits hepatitis C virus replication by preventing a cyclophilin A induced cis-trans isomerisation in domain II of NS5A. PLoS One. 2010 Oct 27;5(10):e13687. [2]. Quarato G, et al. The cyclophilin inhibitor alisporivir prevents hepatitis C virus-mediated mitochondrial dysfunction. Hepatology. 2012 May;55(5):1333-43. [3]. de Wilde AH, et al. Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model. Virus Res. 2017 Jan 15;228:7-13. [4]. Esser-Nobis K, et al. The cyclophilin-inhibitor alisporivir stimulates antigen presentation thereby promoting antigen-specific CD8(+) T cell activation. J Hepatol. 2016 Jun;64(6):1305-14.