Antiviral agents active against human herpesviruses HHV-6, HHV-7 and HHV-8

Abstract

A series of antiviral compounds were examined for their activity against human herpesvirus type 6 (HHV-6), type 7 (HHV-7) and type 8 (HHV-8). They were selected either because they are already approved for clinical use in the treatment of herpesvirus infections (acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, brivudin, foscarnet and cidofovir) or have demonstrated marked activity against herpesviruses (lobucavir, H2G, A-5021, D/L-cyclohexenyl G and S2242). In view of their host cell specificity, different cells and assays had to be used for determining antiviral activity against these three viruses. The most potent compounds with the highest antiviral selectivity index were: (i) for HHV-6; foscarnet, S2242, A-5021 and cidofovir; (ii) for HHV-7; S2242, cidofovir and foscarnet; and (iii) for HHV-8; S2242, cidofovir and ganciclovir. As mycophenolic acid has been shown to enhance significantly the activity of acyclic guanosine analogues (such as acyclovir, penciclovir and ganciclovir) in vitro against HSV-1, HSV-2, VZV and HCMV, it would seem worth evaluating whether mycophenolic acid also potentiates the activity of these acyclic guanosine analogues against HHV-6, -7 and -8.