Search

Hepatitis C virus infection is an important health problem, mostly in transplanted patients, not only because of the high prevalence of the related co-morbidities, but also because the immunosuppressive therapy favors virus replication and interferon-α based antiviral therapy cannot be used. Notably, in contrast to other immunosuppressants, cyclosporine does not increase, but rather may decrease the incidence of some viral infections. As its immunosuppressive action is firmly established, cyclosporine is used to prevent and treat graft-versus-host disease in bone-marrow transplantation and to prevent rejection of kidney, heart, and liver transplants. It is demonstrated that cyclosporine inhibits and even stops HCV replication, having the unique property to act simultaneously both as an immunosuppressive and as an anti-HCV agent. Studies starting from this observation permitted progress in understanding the HCV biology and the discovery of new cyclosporine derivatives with antiviral activity, but deprived of immunosuppressive action. Antiviral effects were seen in case of NIM8111 and Debio-025, non-immunosuppressive cyclosporine derivatives. The viral replication is dependent on cyclophilins, a vulnerability the cyclophilin inhibitors might take advantage of. The non-immunosuppressant analogues showed a close correlation between the inhibition of viral replication and cyclophilin binding, which made cyclophilin a potential target for antiviral compounds. However, the recent development of more efficient anti-HCV agents will probably hamper this promising line of research. [ABSTRACT FROM AUTHOR]