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 (ACVp2ACV) with a higher water solubility. ACVp2ACV markedly inhibited HSV-1 replication in Vero cells [50% effective concentration (EC50) of 2.8M vs. 6.6M for ACV] and was non-toxic in the cells at concentrations .15M. ACVp2ACV 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, ACVp2ACV acts as an effective antiviral prodrug against HSV-1.
A new homodimer of acyclovir as a prodrug with increased solubility and antiviral activity
BRANDI, GIORGIO;ROSSI, LUIGIA;SCHIAVANO, GIUDITTA FIORELLA;MAGNANI, MAURO
2009
Abstract
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 (ACVp2ACV) with a higher water solubility. ACVp2ACV markedly inhibited HSV-1 replication in Vero cells [50% effective concentration (EC50) of 2.8M vs. 6.6M for ACV] and was non-toxic in the cells at concentrations .15M. ACVp2ACV 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, ACVp2ACV acts as an effective antiviral prodrug against HSV-1.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
