Poly complex antiviral activity

Kiselev O, Kozeletskaya K, Melenevskaya E et al. (1998a) The antiviral activity of the complex of fullerene C60 with poly(N-vinyl-pyrrolidone). Mol Mat. 11 121-124. 

Kiselev O, Kozeletskaia KN, Melenevskaia EYu et al. (1998b) Antiviral activity of fullerene (60 )C complexed with poly(N-vinylpyrrolidone). Dokl AkadNauk. 361 547-549 (Russian). 

The relatively greater importance of poly(I) than of poly(C) in the antiviral activity of poly(I) poly(C) has further been demonstrated in experiments in which the two components were added sequentially to cell cultures122-124). Sequential administration of the homopolymers in the order poly(I) followed by poly(C) led to an equal or greater interferon response than obtained after addition of poly(I) poly(C) itself. However, when the homopolymers were added in the order poly(C) -> poly(I) the antiviral activity of the complex was only partially restored. The mechanism by which the order of addition of... 

Most of the compounds mentioned above are electrically neutral and therefore poorly soluble in water at neutral pH. There are exceptions, such as poly (9-vinyladenine), and poly(l-vinyluracil). All compounds are stable to chemical and enzymatic hydrolysis, and they form complexes with complementary polynucleotides. However, these complexes do not have the simple stoichiometry found in natural nucleic acids. Stability and stoichiometry of complexes do depend on solvent, temperature, and pH of the system (36). Again, because of the complexity of the field, the reader is referred to the review articles mentioned above (36-38). Poly(A -vinyl) derivatives have been carefully tested for their biological and antiviral activity by Pitha (38) in enzyme assays, cell cultures, and in organisms. 

In short, poly rI poly rC and other polynucleotides designed to induce interferon failed to demonstrate substantial antiviral or anticancer activities at doses that did not produce unacceptable toxicities. The mechanisms resulting in the toxicities are still not clearly understood. Complex formation with polycations altered pharmacokinetic properties but did not enhance efficacy and probably exacerbated toxicities. 

Theoretically, it may be possible to artificially increase the production of interferon by the action of an inducer. Synthetic double-stranded ribonucleotide polymers, in particular the double-helical complex of polyinosinic acid with poly-cytidylic acid RNA (poly IC) are used in this way These agents activate the synthesis of interferon. They increase the resistance to viruses of cells m culture, and promote recovery in rabbits suffering from herpetic eye infection. This type of activity is an important prospect in the field of antiviral therapy. 

---