Effect of increasing thiolation of the polycytidylic acid strand of poly I:poly C on the α, β and γ interferon-inducing properties, antiviral and antiproliferative activities

Kailash C. Chadha, Wlodzimierz E. Dembinski, Christopher B. Dunn, Janos Aradi, Thomas J. Bardos, Joseph A. Dunn, Julian L. Ambrus

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5 Citations (Scopus)

Abstract

Double-stranded RNAs induce interferons and cause the development of antiviral and antiproliferative activities. Antiviral activity is related to the production of interferons and other proteins that stimulate various immunologic activities, which appear to contribute to their overall antiproliferative activity. The most active double-stranded RNA, polyI:polyC, was shown to be too toxic for therapeutic use. We conducted selective thiolation of the polyC strand at the five position of the cytosine bases, generating a partially thiolated polyC (MPC) which after annealing with a complimentary unmodified polyI, gave the thiolated double-stranded RNA, pI:MPC. We have explored antiviral and antiproliferative activities at various levels of thiolation and found that optimal responses can be obtained at 7.4% level of thiolation. This compound deserves further study of antiviral and antiproliferative responses in vivo, and eventually clinical exploration. Earlier studies have shown that this and related compounds are active against HIV-1, in human cells, and against DNA polymerases of DNA and RNA tumor viruses.

Original languageEnglish
Pages (from-to)171-177
Number of pages7
JournalAntiviral Research
Volume64
Issue number3
DOIs
Publication statusPublished - Dec 1 2004

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Keywords

  • AIDS
  • Antiviral agents
  • Cellular proliferation
  • HIV-1 infection
  • Interferon(s)-α, -β, -γ
  • Thiolated polyI:polyC
  • Vesicular stomatitis virus (VSV)
  • dsRNA

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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