Cyclophilin family (Cyp)

The cyclophilin family comprises a group of highly conserved proteins with peptidyl-prolyl cis-trans isomerase (PPIase) activity, which is essential for protein folding and cellular signaling. Cyclophilin A (CypA), the most abundant member, is a key host factor for several viruses, including Hepatitis C virus (HCV) and HIV-1, where it facilitates viral replication and assembly by interacting with viral proteins. Other members, such as Cyclophilin D, regulate mitochondrial permeability and are involved in cell death pathways. Therapeutic targeting of the cyclophilin family, particularly with non-immunosuppressive inhibitors like SCY-116, aims to treat viral infections and inflammatory conditions by blocking these interactions without the side effects of traditional immunosuppressants like cyclosporine A. These inhibitors typically bind to the PPIase active site, preventing the enzymatic activity and protein-protein interactions necessary for disease progression. In viral diseases, cyclophilin inhibition disrupts the formation of the viral replication organelle and the stability of the viral capsid. Beyond virology, cyclophilins are implicated in cancer, cardiovascular disease, and neurodegeneration, making them versatile therapeutic targets. The development of isoform-selective or non-immunosuppressive cyclophilin inhibitors represents a significant advancement in minimizing off-target effects while maintaining therapeutic efficacy.

Other names

Peptidyl-prolyl cis-trans isomerase familyPPIase familyImmunophilin familyCyclophilin

Inhibition of the peptidyl-prolyl cis-trans isomerase (PPIase) activity of cyclophilins, which prevents the folding and assembly of viral proteins and host factors required for viral replication and other pathological processes.