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Molecular Pharmacology, Vol 11, 61-69, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Antiviral Activity of Partially Thiolated Polynucleotides

J. A. O’MALLEY 1, Y. K. HO 1, P. CHAKRABARTI 1, L. DIBERARDINO 1, P. CHANDRA 1, D. A. O. ORINDA 1, D. M. BYRD 1, T. J. BARDOS 1, and W. A. CARTER 1

1 Departments of Medical Viral Oncology, Roswell Park Memorial Institute 14203, and Medicinal Chemistry, State University of New York at Buffalo, Buffalo, New York 14214, and University of Frankfurt Medical School, Frankfurt, Germany

Structural modification of poly(I)·poly(C) (thiolation of position 5 of some of the cytosine bases in polycytidylate) produces compounds which induce antiviral activity in both human and murine cells. Since increasing degrees of thiolation increase nuclease resistance, this study reaffirms the notion that enhanced nucleolytic resistance of double-stranded RNAs is not a critical property for interferon induction. Depletion of the full expression of the antiviral state in human cells occurred after washing the cells shortly after poly(I)·poly(C) exposure; addition of fresh poly(I)·poly(C) did not restore full antiviral function to the washed cells. However, prior treatment with thiolated complexes abolished this depletion. The thiolated polymers may prove to be useful in circumventing the hyporesponsiveness usually seen after repeated stimulation with the interferon inducer poly(I)·poly(C), in experimental viral infections.

Submitted on July 23, 1974




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