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

Abstract

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.