A new homodimer of aciclovir as a prodrug with increased solubility and antiviral activity.

Aciclovir (ACV) is the drug of choice against herpes simplex virus type 1 (HSV-1) infection. However, its limited solubility in water and limited oral bioavailability represent the main limitations of this drug. Utilising a plaque reduction assay, this study assessed the antiherpetic activity of a new homodimer of ACV (ACVp(2)ACV) with a higher water solubility. ACVp(2)ACV markedly inhibited HSV-1 replication in Vero cells [50% effective concentration (EC(50)) of 2.8 microM vs. 6.6 microM for ACV] and was non-toxic in the cells at concentrations <or= 15 microM. ACVp(2)ACV encapsulated in erythrocytes provides effective protection against HSV-1 replication in human macrophages and also partially against the HSV-1 thymidine kinase-deficient strain. Thus, ACVp(2)ACV acts as an effective antiviral prodrug against HSV-1.