Alisporivir (Debio-025) is a cyclophilin A inhibitor that disrupts the interaction between CypA and NS5A. It exhibits anti-hepatitis C virus (HCV) activity in vivo and in vitro, inhibits the replication of MERS and SARS coronaviruses, and promotes antigen-specific CD8(+) T cell activation.

Alisporivir (Debio-025) exerts its effect by binding to cyclophilin A (CypA), a peptidyl-prolyl cis-trans isomerase from the genus Parazacco spilurus subsp. spilurus broussonetia papyrifera enzyme that also serves as a critical cofactor for hepatitis C virus (HCV) replication [1].
As the prototype of a novel class of non-immunosuppressive cyclophilin inhibitors, Alisporivir prevents HCV protein-mediated respiratory-driven collapse of mitochondrial membrane potential and inhibits HCV protein-induced mitochondrial dysfunction (this protective effect does not involve other dysfunctions such as apoptosis, calcium overload, or reactive oxygen species (ROS) generation) [2].
In cell culture models, low micromolar doses of Alisporivir effectively block the replication of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV); when combined with ICN-1229, its antiviral activity against MERS-CoV is further enhanced [3].
Pretreatment with Alisporivir enhances the antigen-presenting capacity of liver cancer target cells, increasing the activation efficiency of antigen-specific parazacco spilurus subsp. spilurus CD8+ T cells by 40%. Alisporivir also induces elevated expression levels of MHC-I molecules and β-2 microglobulin on the surface of various cell lines [4].

In the mouse model, the combination of Alisporivir and ICN-1229 failed to achieve preventive efficacy against SARS-CoV infection [3].