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

Abstract 

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±1.06μM. 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.

Abbreviations: ART, artesunate, DMSO, dimethyl sulfoxide, EBV, Epstein–Barr virus, FCS, fetal calf serum, GCV, ganciclovir, HCMV, human cytomegalovirus, HFFs, human foreskin fibroblasts, HHV-6, human herpesvirus 6, HHV-6A/B, human herpesvirus 6 variant A/B, HSV-1, herpes simplex virus type 1, IC₅₀, mean inhibitory concentration 50%, LDH, lactate dehydrogenase, MDCK, Madin-Darby canine kidney, PBS, phosphate-buffered saline, PRA, plaque reduction assay, qPCR, quantitative real-time PCR, ValGCV, valganciclovir

Keywords: Human herpesvirus 6, Human cytomegalovirus, Epstein–Barr virus, Artesunate, Artemisinin, Antiviral activity