Effect of increasing thiolation of the polycytidylic acid strand of poly I:poly C on the alpha, beta and gamma interferon-inducing properties, antiviral and antiproliferative activities.

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.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

Chadha KC,Dembinski WE,Dunn CB,Aradi J,Bardos TJ,Dunn JA,Ambrus JL Sr

doi

10.1016/j.antiviral.2004.08.002

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

171-7

issue

3

eissn

0166-3542

issn

1872-9096

pii

S0166-3542(04)00165-2

journal_volume

64

pub_type

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