Aciclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), and varicella-zoster virus (VZV).
The inhibitory activity of Aciclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts aciclovir into aciclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In vitro, aciclovir triphosphate stops replication of the herpes viral DNA. This is accomplished in three ways: 1) competitive inhibition of viral DNA polymerase; 2) incorporation into and termination of the growing viral DNA chain; and 3) inactivation of the viral DNA polymerase. The greater antiviral activity of aciclovir against HSV compared with VZV is due to its more efficient phosphorylation by the viral TK.