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

Giorgio Brandi (1) , Luigia Rossi (2) , Giuditta F. Schiavano (1) , Enrico Millo (3) , Mauro Magnani (2)

1 Hygiene Section
2 Biochemistry and Molecular Biology Section
3 Department of Experimental Medicine

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 (ACVpACV) with a higher water solubility. ACVpACV markedly inhibited HSV-1 replication in Vero cells [50% effective concentration (EC) of 2.8μM vs. 6.6μM for ACV] and was non-toxic in the cells at concentrations ≤15μM. ACVpACV 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, ACVpACV acts as an effective antiviral prodrug against HSV-1.

Mots clés: Antiviral prodrug; Aciclovir homodimer; Anti-HSV-1 activity

Giorgio Brandi, Luigia Rossi, Giuditta F. Schiavano, Enrico Millo, Mauro Magnani. A new homodimer of aciclovir as a prodrug with increased solubility and antiviral activity. International Journal of Antimicrobial Agents, 2009, 34 (2), pp.177. ⟨10.1016/j.ijantimicag.2009.02.025⟩. ⟨hal-00556335⟩