Effect of (r)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (H2G) and AZT-lipid-PFA on human herpesvirus-6B infected cells

Background: Human herpesvirus-6 (HHV-6) has been associated with a wide spectrum of diseases. (r)-9-[4-Hydroxy-2-(hydroxymethyl)butyl]guanine (H2G) is an acyclic guanosine analogue that is structurally similar to acyclovir and is in clinical development for treatment of herpesvirus infections. H2G has been found to have activity against HSV type 1, HSV type 2, and HHV-6 in lymphoblast cell lines. A new anti-viral duplex drug, 3'-azido-3'-deoxythymidylyl-(5' -> 2-O)-3-O-octadecyl-sn-glycerol (AZT-lipid-PFA), linking zidovudine (AZT) and foscarnet (PFA) via a lipophilic octadecylglycerol residue (lipid) also exhibits antiviral activities against HIV, HSV type I and HCMV. Objective: To assess the efficacy of H2G and AZT-lipid-PFA conjugate against HHV-6. Study design: Drug-associated toxicity and proliferative response were evaluated. We conducted in vitro experiments to determine the efficacy of H2G and an AZT-lipid-PFA conjugate in interfering with expression HHV-6 viral transcript in primary human peripheral blood mononuclear cells (PBMC). Results: Both H2G and AZT-lipid-PFA were effective at inhibiting expression of HHV-6 gene transcript at comparable concentrations. Additionally, while AZT-lipid-PFA treatment was toxic to cells at concentrations above 5 mu M, H2G treatment was associated with minimal cytotoxicity. Conclusion: These data suggest the potential application of these anti-viral compounds in controlling HHV-6 infection. (C) 2009 Published by Elsevier B.V.