OLIGONUCLEOTIDE DERIVATIVES SUPPRESS TRANSCRIPTION OF INFLUENZA-VIRUS RNA

A study was made of inhibition of virus RNA transcription in vitro and synthesis of virus proteins in cells infected with flu virus, using oligonucleotide derivatives d(T)3, d(T)4, d(T)g, d(T)10, d(CCAAACA), d(TCACCCTC), d(TTCCCATT), d(AATACTCT) and d(TCACCCTCTTCCCATT), which carry residues of ethidium (Et), deutroporphyrin (DDP) and its complexes with Fe3+, hemin (Hem), cholesterol (Chs), deuterotestosterone (Hst), estrone (ES), and naphthoquinone (NQn) at the 5'-end and/or 3'-end phosphate. Unmodified oligonucleotides and their derivatives suppressed cell protein synthesis only negligibly, but inhibited synthesis of flu virus proteins. Most of the structural modifications increased the inhibiting effect of oligonucleotides. Oligonucleotide derivatives carrying residues of porphyrin, quinone, ethidium, cholesterol, deuterotestosterone, and estrone at concentrations in the order of 10 muM suppressed virus development by 50-80%. Some deuteroporphyrin, cholesterol, and ethidium derivatives retain a marked inhibition effect (20-50%) even at concentrations of 0.1 muM. Our data indicate that flu virus development is inhibited by the interaction between oligonucleotide derivatives and proteins of the transcription complex. Abbreviations used: Et' and Et'', ethidium; DDP, deuteroporphyrin (IX); Hem, hemin; Chs, cholesterol; Es, estrone; NQn, naphthoquinone; His, histidine; Hts, deuterotestosterone; cap, 7-Met-Gp3A.