Mechanism of action of acyclic nucleoside phosphonates against herpes virus replication

Foremost among the acyclic nucleoside phosphonates currently pursued for their potential in the treatment of herpes and retrovirus infections are (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA). These compounds are as such taken up by the cells and then phosphorylated by cellular enzymes to their diphosphoryl derivatives HPMPCpp and PMEApp. The main target for the antiviral action of HPMPCpp and PMEApp is the viral DNA polymerase. Whereas PMEApp has been shown to interact as a DNA chain terminator with both retro- and herpes viruses, the mechanism by which HPMPCpp inhibits herpes viral DNA synthesis remains the subject of further study.