Comparison of antiviral compounds against human herpesvirus 6 and 7

Mariko Yoshida, Masao Yamada, Takashi Tsukazaki, Subhendra Chatterjee, Fred D. Lakeman, Shiro Nii, Richard J. Whitley

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Abstract

Four classes of antiviral compounds were evaluated for inhibitory activity against two variants of human herpesvirus 6 (HHV-6A and -6B) and human herpesvirus 7 (HHV-7). These included: (1) a pyrophosphate analog, phosphonoformic acid (PFA); (2) beta-guanine analogs, 9-(2-hydroxyethoxymethyl)guanine (acyclovir or ACV), 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (ganciclovir or GCV) and 9-(4-hydroxy-3-hydroxy-3-hydroxymethylbutylyl)guanine (penciclovir or PCV); (3) acyclic nucleoside phosphonates, (S)-1-[(3-hydroxy-2-phosphonylmethoxy)propyl]cytosine [cidofovir or (S)-HPMPC] and its cyclic derivative (S)-cyclic-HPMPC (cHPMPC), 9-[[2-hydroxy-1-phosphonomethoxy)ethoxy]methyl]guanine (HPMEMG) and 9-[(2-phosphonylmethoxy)ethyl]-2,6-diaminopurine (PMEDAP), and the seven other related compounds; and (4) a series of benzimidazole ribonucleosides, including 2-bromo-5,6-dichloro-1-(beta-d-ribofuranosyl)benzimidazole (BDCRB). End-point inhibitory concentration (EPC) and 50% effective inhibitory concentration (EC50) values were determined by a dot-blot antigen detection method in cord blood mononuclear cells infected with HHV-6A, HHV-6B or HHV-7 at a multiplicity of infection of 0.004 CCID50/cell. (S)-HPMPC and cHPMPC had an EC50 value of approximately 0.3 μg/ml for HHV-6A, 1.2 μg/ml for HHV-6B and 3.0 μg/ml for HHV-7. These compounds were the most active of those tested against each virus. The EC50 value of GCV for HHV-6A was 0.65 μg/ml, 1.33 μg/ml for HHV-6B, and >7 μg/ml for HHV-7. The EC50 values of ACV and PCV were approximately 6-8 μg/ml for HHV-6A, 16-24 μg/ml for HHV-6B and 121-128 μg/ml for HHV-7. These drugs were the least active. The sensitivity of HHV-7 to the guanine analogs was different from HHV-6, suggesting a difference in selectivity of specific viral enzymes. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)73-84
Number of pages12
JournalAntiviral Research
Volume40
Issue number1-2
DOIs
Publication statusPublished - Dec 1 1998

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Keywords

  • Antiviral compounds
  • Benzimidazole ribonucleosides
  • Dot-blot method
  • Human herpesvirus 6
  • Human herpesvirus 7
  • Virus replication

ASJC Scopus subject areas

  • Pharmacology
  • Virology

Cite this

Yoshida, M., Yamada, M., Tsukazaki, T., Chatterjee, S., Lakeman, F. D., Nii, S., & Whitley, R. J. (1998). Comparison of antiviral compounds against human herpesvirus 6 and 7. Antiviral Research, 40(1-2), 73-84. https://doi.org/10.1016/S0166-3542(98)00049-7