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.
Brandi
Giorgio
G
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy. giorgio.brandi@uniurb.it
Rossi
Luigia
L
Schiavano
Giuditta F
GF
Millo
Enrico
E
Magnani
Mauro
M
D000212:Acyclovir / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology*; D012995:Solubility; D014709:Vero Cells; D010948:Viral Plaque Assay / Q000379:methods; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D011355:Prodrugs; D000212:Acyclovir