Antiviral properties of polyinosinic acids containing thio and methyl substitutions.
Polyinosinic acids containing methyl and sulphur substitutions are potent inhibitors of reverse transcriptase. Substitution of sulphur for oxygen at the 6 position produces significant effects on the properties of polyinosinic acid: the kinetics of inhibition change from competitive to mixed-type and the inhibition constant falls by three orders of magnitude. In contrast, 1-methyl substitution produces no such effects. Poly(1-methyl-6-thioinosinic acid) or poly(m1s6I) inhibits irreversibly, inhibiting all ten reverse transcriptases tested under a variety of assay conditions. In cell culture test systems, poly(m1s6I) is capable of blocking both infection by non-transforming viruses and transformation by a sarcoma virus. The presence of poly(m1s6I) in a preinfected culture results in the production of non-infectious virus particles lacking reverse transcriptase activity.
D009189:Avian Myeloblastosis Virus / Q000187:drug effects; D017988:Gammaretrovirus / Q000187:drug effects; D005256:Leukemia Virus, Feline / Q000187:drug effects; D011069:Poly I / Q000494:pharmacology*; D011131:Polyribonucleotides / Q000494:pharmacology*; D012190:Retroviridae / Q000187:drug effects* / Q000201:enzymology; D018894:Reverse Transcriptase Inhibitors; D012842:Sarcoma Virus, Woolly Monkey / Q000187:drug effects; D013329:Structure-Activity Relationship; D013873:Thionucleotides / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D011131:Polyribonucleotides; D018894:Reverse Transcriptase Inhibitors; D013873:Thionucleotides; D011069:Poly I; C019533:poly(1-methylinosinic acid); C032133:poly(thioinosinic acid); C032134:poly(1-methyl-6-thioinosinic acid)