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Gebhardt BM, Focher F, Eberle R, et al. Effect of combinations of antiviral drugs on herpes simplex encephalitis. Drug Des Devel Ther. 2009;3:289-94doi: 10.2147/dddt.s8133.
Gebhardt, B. M., Focher, F., Eberle, R., Manikowski, A., & Wright, G. E. (2009). Effect of combinations of antiviral drugs on herpes simplex encephalitis. Drug design, development and therapy, 3289-94. https://doi.org/10.2147/dddt.s8133
Gebhardt, Bryan M, et al. "Effect of combinations of antiviral drugs on herpes simplex encephalitis." Drug design, development and therapy vol. 3 (2009): 289-94. doi: https://doi.org/10.2147/dddt.s8133
Gebhardt BM, Focher F, Eberle R, Manikowski A, Wright GE. Effect of combinations of antiviral drugs on herpes simplex encephalitis. Drug Des Devel Ther. 2009 Dec 29;3:289-94. doi: 10.2147/dddt.s8133. PMID: 20054446; PMCID: PMC2802127.
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Drug Des Devel Ther. 2009 Dec 29;3:289-94. doi: 10.2147/dddt.s8133.

Effect of combinations of antiviral drugs on herpes simplex encephalitis.

Drug design, development and therapy

Bryan M Gebhardt, Federico Focher, Richard Eberle, Andrzej Manikowski, George E Wright

Affiliations

  1. LSU Eye Center, Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.

PMID: 20054446 PMCID: PMC2802127 DOI: 10.2147/dddt.s8133

Abstract

2-Phenylamino-6-oxo-9-(4-hydroxybutyl)purine (HBPG) is a thymidine kinase inhibitor that prevents encephalitic death in mice caused by herpes simplex virus (HSV) types 1 and 2, although its potency is somewhat less than that of acyclovir (ACV). The present study was undertaken to determine the effect of combinations of HBPG and either ACV, phosphonoformate (PFA), or cidofovir (CDF) against HSV encephalitis. BALB/c mice were given ocular infections with HSV-1 or HSV-2, and treated twice daily intraperitoneally for five days with HBPG, alone or in combination with ACV, PFA, or CDF. Animals were observed daily for up to 30 days, and the day of death of each was recorded. All of the combinations showed additivity, and the combination of HBPG + ACV appeared to be synergistic, ie, protected more mice against HSV-1 encephalitis compared with each drug given alone. Delay of treatment with HBPG for up to two days was still effective in preventing HSV-2 encephalitis. The combination of the thymidine kinase inhibitor HBPG and the antiherpes drug ACV may have synergistic activity against HSV encephalitis. The development of a potent and safe combination therapy for the prevention and/or treatment of HSV infection of the central nervous system can improve the outcome of this infection in humans.

Keywords: antivirals; herpetic encephalitis

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