UNUSUAL SINGLE-STRANDED POLYRIBONUCLEOTIDES AS POTENT ANTI-HIV AGENTS

Polyribonucleotides (PMTG and PMTI) containing 1-methyl-6-thioguanosin e or 1-methyl-6-thioinosine, respectively, as the sole nucleoside comp onent are shown to be potent inhibitors of various strains of HTV-1 an d HTV-2 in a number of human lymphocyte and macrophage cell lines in t issue culture as well as in fresh human peripheral blood lymphocytes a nd macrophages. PMTI and PMTG exhibit potencies in the range of 10(-7) -10(-8) M in these systems. The polynucleotides are active against vir us strains resistant to AZT and pyridinone derivatives. Both PMTI and PMTG are synergistic with AZT and with ddI, and both inhibit HIV rever se transcriptase at nanomolar concentrations. The polymers show little or no toxicity in human cell lines at the highest doses tested (100 m u g/mL, or about 0.2-1 mu M). This class of compounds represents a new lead in AIDS therapeutic drug discovery.