[The terminase complex, a relevant target for the treatment of HCMV infection]

Abstract

Human cytomegalovirus (HCMV) is an important ubiquitous opportunistic pathogen that belongs to the betaherpesviridae. Primary HCMV infection is generally asymptomatic in immunocompetent individuals. In contrast, HCMV infection causes serious disease in immunocompromised patients and is the leading cause of congenital viral infection. Although they are effective, the use of conventional molecules is limited by the emergence of resistance and by their toxicity. New antivirals targeting other replication steps and inducing fewer adverse effects are therefore needed. During HCMV replication, DNA packaging is performed by the terminase complex, which cleaves DNA to package the virus genome into the capsid. With no counterpart in mammalian cells, these terminase proteins are ideal targets for highly specific antivirals. A new terminase inhibitor, letermovir, recently proved effective against HCMV in phase III clinical trials. However, its mechanism of action is unclear and it has no significant activity against other herpesvirus or non-human CMV.