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.


METHODS
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 IC(50) values by immunofluorescence or plaque reduction assays.


RESULTS
Sensitivity of HHV-6 to artesunate was demonstrated with an IC(50) of 3.80+/-1.06microM. This is in a range similar to IC(50) 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.
Milbradt
Jens
J
Institute for Clinical and Molecular Virology, Medical Center Erlangen, University of Erlangen-Nuremberg, Germany. jens.milbradt@viro.med.uni-erlangen.de
Auerochs
Sabrina
S
Korn
Klaus
K
Marschall
Manfred
M
D000998:Antiviral Agents / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002478:Cells, Cultured; D019085:Fluorescent Antibody Technique, Direct; D006564:Herpesviridae / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D037621:Artemisinins; D014764:Viral Proteins; D000077332:Artesunate