Novel inhibitors of human CMV

Abstract

Human CMV (HCMV) is an opportunistic pathogen associated with significant morbidity and mortality among immunocompromised patients (in particular immunosuppressed patients with stem cell or solid organ transplantation, AIDS or cancer). Additionally, congenital HCMV infections are a leading cause of birth defects and infections in children, occurring in 1 to 2% of all live births. Drugs currently available for the treatment of HCMV diseases in the immunocompromised individual include ganciclovir, its oral prodrug valganciclovir, cidofovir, foscavir and fomivirsen. Although these drugs have proved successful in the management of HCMV disease in immunocompromised patients, their use is limited because of toxicity, poor oral bioavailability, modest efficacy and the development of drug resistance. Furthermore, no drug has been licensed for use in the treatment of congenital HCMV. Therefore, there is a need to develop new compounds against HCMV diseases. The search for novel inhibitors of HCMV replication has led to the identification of new molecular targets such as the viral protein kinase UL97, and the viral proteins involved in genome replication or in DNA maturation and egress. Moreover, a new strategy based on the identification of specific cellular targets required for viral replication has been developed. This review focuses on non-nucleoside compounds that inhibit specific viral processes and on cell-based approaches that result in the selective inhibition of virus replication.