Sensitivity of human herpesvirus 6 and other human herpesviruses to the broad-spectrum antiinfective drug artesunate

Background: Antiviral therapy for HHV-6 infection with conventional anti-herpesviral drugs is problematic so novel drugs are required. Artesunate is a well-tolerated drug approved for malaria therapy which possesses antiviral activity. Objective: The artesunate sensitivity of HHV-6 was analyzed and compared to that of several other human herpesviruses. Study design: Cultured human cells were productively infected with strains of HHV-6 or other human herpesviruses to measure artesunate inhibition of viral protein synthesis (Western blot analysis) or viral genome replication (qPCR), and to determine IC50 values by immunofluorescence or plaque reduction assays. Results: Sensitivity of HHV-6 to artesunate was demonstrated with an IC50 of 3.80 +/- 1.06 mu M. This is in a range similar to IC50 values for HCMV and EBV. Artesunate treatment of HHV-6-infected cells significantly reduced viral early and late protein synthesis that occurred in the absence of drug-induced apoptosis or necrotic cytotoxicity. HHV-6A genome replication was markedly reduced by artesunate. Conclusions: Artesunate possesses anti-HHV-6 activity in vitro and may be useful for treatment of HHV-6 infections. (C) 2009 Elsevier B.V. All rights reserved.