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Molecular Pharmacology

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Research ArticleArticle

Antiviral Activity of Poly(7-deazainosinic acid)-Derived Complexes in Vitro and in Vivo

E. DE CLERCQ, V. G. EDY, P. F. TORRENCE, J. A. WATERS and B. WITKOP
Molecular Pharmacology November 1976, 12 (6) 1045-1051;
E. DE CLERCQ
Rega Institute for Medical Research, University of Leuven, Leuven, Belgium, and Laboratory of Chemistry, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health, Bethesda, Maryland 20014
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V. G. EDY
Rega Institute for Medical Research, University of Leuven, Leuven, Belgium, and Laboratory of Chemistry, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health, Bethesda, Maryland 20014
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P. F. TORRENCE
Rega Institute for Medical Research, University of Leuven, Leuven, Belgium, and Laboratory of Chemistry, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health, Bethesda, Maryland 20014
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J. A. WATERS
Rega Institute for Medical Research, University of Leuven, Leuven, Belgium, and Laboratory of Chemistry, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health, Bethesda, Maryland 20014
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B. WITKOP
Rega Institute for Medical Research, University of Leuven, Leuven, Belgium, and Laboratory of Chemistry, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health, Bethesda, Maryland 20014
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Abstract

The antiviral activities and/or interferon-inducing abilities of poly(I)·poly(C), poly(I)·poly(br5C), poly(c7I)·poly(C), and poly(c7I)·poly(br5C) have been assessed in a variety of cell cultures (human, rabbit, and mouse) and animals (rabbits, mice). In cultured cells the compounds were also examined for inhibition of host cell macromolecule synthesis. Lethal effects were looked for in mice sensitized with lead acetate. Although the extent of antiviral activity of the polymers varied from one assay system to another, the following order of (decreasing) activity appeared applicable to all systems: poly(I)·poly(br5C) [unknown] poly(I)·poly(C) > poly(c7I)·poly(b5C) [unknown] poly(c7I)·poly(C). Poly(I)·poly(C) and poly(I)·poly(br5C) did not differ markedly in antiviral activity, interferon-inducing ability, or toxicity. However, in human skin fibroblasts, poly(I)·poly(br5C) was distinctly superior as an interferon inducer, especially at lower doses. Poly(c7I)·poly(C) was the least active of the four polymers and was also the most potent inhibitor of host cell macromolecule synthesis. Poly(c7I)·poly(br5C) equaled or even surpassed poly(I)·poly(C) in interferon-inducing activity in human skin fibroblasts; in animals, however, it proved definitely less active. In determining the antiviral behavior of the complexes studied, two effector mechanisms should be taken into account: interferon induction and inhibition of macromolecule biosynthesis. Which of these parameters will predominate would ultimately depend on the fate of the double-stranded complex after it has reacted with the cell.

ACKNOWLEDGMENTS The skillful technical assistance of Anita Van Lierde and Miette Stuyck and the editorial help of Janine Putzeys are gratefully acknowledged. The authors are indebted to Dr. Leonard Kohn, National Institutes of Health, for his help in determining sedimentation coefficients.

  • Copyright © 1976 by Academic Press, Inc.

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Molecular Pharmacology
Vol. 12, Issue 6
1 Nov 1976
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Research ArticleArticle

Antiviral Activity of Poly(7-deazainosinic acid)-Derived Complexes in Vitro and in Vivo

E. DE CLERCQ, V. G. EDY, P. F. TORRENCE, J. A. WATERS and B. WITKOP
Molecular Pharmacology November 1, 1976, 12 (6) 1045-1051;

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Research ArticleArticle

Antiviral Activity of Poly(7-deazainosinic acid)-Derived Complexes in Vitro and in Vivo

E. DE CLERCQ, V. G. EDY, P. F. TORRENCE, J. A. WATERS and B. WITKOP
Molecular Pharmacology November 1, 1976, 12 (6) 1045-1051;
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