Antiviral activity of diverse classes of broad-acting agents and natural compounds in HHV-6-infected lymphoblasts

Background: HHV-6 replication requires complex and poorly understood interactions between viral and cellular factors. Objectives: Several natural compounds or broad-acting pharmacological agents were studied in an attempt to discover new targets for anti-HHV-6 therapy. Study design: The antiviral activity was determined in human T-lymphoblasts, using HHV-6A (GS)-infected HSB-2 cells, HHV-6B (Z29)-infected MOLT-3 cells and HHV-6B (HST)-infected MT4 cells. Virus replication was measured by CPE and qPCR assay. Foscarnet was included as the reference compound. Results: Among the 15 natural compounds tested, only 'red marine algae' (an extract rich in sulfated polysaccharides) exhibited strong activity when added during virus adsorption. Among the broad-acting pharmacological agents, chloroquine, artemisinin, hypericin, ribavirin, resveratrol and glycyrrhizic acid were all inactive. Amantadine produced a reproducible inhibition of HHV-6 replication, albeit at relatively high concentrations. Except for lamotrigine, which was moderately active against HHV-6B, several antiepileptic drugs were shown to have no activity. We included several compounds which we previously described as potent HHV-6 inhibitors, i.e., the non-nucleoside inhibitor CMV423 and the acyclic nucleoside phosphonate analogues cidofovir and 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-3-deazaadenine. The latter compound exhibited remarkable anti-HHV-6 activity. Conclusion: Further optimization of compounds belonging to diverse classes of antiherpetic agents, for their specific action against HHV-6, is warranted. (c) 2006 Elsevier B.V All rights reserved.