Inhibition of the synthesis of Moloney leukemia virus structural proteins by N-methylisatin-beta-4',4'-diethylthiosemicarbazone

Abstract

The mechanism of inhibition of Moloney leukemia virus by N-methylisatin-beta-4',4'-diethylthiosemicarbazone was studied. Experiments that used [3H]leucine for short-pulse labeling in the presence of the drug resulted in a 71% inhibition in the synthesis of Pr-80, the polypeptide precursor of the gag viral proteins. The radioactive pulse products of the polypeptide precursors after a further 2-h chase period showed a normal cleavage of the precursors, with the formation of a reduced amount of final mature viral structural proteins. The experimental evidence indicated that at the inhibitory concentration of 17 microM N-methylisatin-beta-4',4'-diethylthiosemicarbazone, the amount of intracellular viral RNA was not affected, whereas the activities of reverse transcriptase and the other viral protein syntheses were suppressed.

N-methylisatin-beta-4',4'-diethylthiosemicarbazone, an inhibitor of Moloney leukemia virus protein production: characterization and in vitro translation of viral mRNA

“…Although the level of viral RNA within the infected cells was not reduced, the synthesis of the MLV structural polyprotein precursors gag and env was inhibited (18,19). In the present study we show that in a cell-free translation system the M-IBDET exerts its effect by direct and specific inhibition of MLV mRNA translation.…”

“…( (19). Immunoprecipitates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (12) followed by fluorography (6).…”

Inhibition of Feline Immunodeficiency Virus Production and HIV Tat Activity by Thiosemicarbazone Derivatives

“…We were the first to show that M-IBDET inhibits the production of M-MuLV Sherman et al, 1980), a member of the retrovirus family. It was shown that M-IBDET specifically inhibits M-MuLV structural protein synthesis by blocking the translation process of M-MuLV mRNA (Ronen and Teitz, 1984;Ronen et al, 1985Ronen et al, , 1987 In an attempt to understand the inhibition of FIV by the TSCD, we examined the effect of A-IBDAT on the synthesis of the FIV gag gene encoding p24 protein. Our pulse-labelling experiments showed that the drug is involved in inhibition of this protein synthesis, and the degree of inhibition is proportional to the druq concentration.…”

“…We have therefore synthesized new TSCD which have antiretroviral activity with the object of choosing those TSCD that have minimal effects on cell growth and the highest therapeutic index (TI) (Teitz et al, 1994). The mechanism of retroviral inhibition was shown to act at the level of viral mRNA translation (Ronen and Teitz, 1984;Ronen et al, 1985Ronen et al, , 1987. Recently, we have also described the selective repression by M-IBDET and A-IBDAT of v-abl-coded protein, an oncogene product associated with tyrosine kinase activity (Teitzet al, 1993).The efficacy ofthe TSCD was tested in feline T-Iymphocytes chronically infected with feline immunodeficiency virus (FIV).…”

Selective repression of v-abl-encoded protein by N-methylisatin-beta-4',4'-diethylthiosemicarbazone and N-allylisatin-beta-4',4'-diallylthiosemicarbazone

“…N-Methylisatin-P-4',4'-diethylthiosemicarbazone (M-IBDET) at concentrations between 3.4 and 34 p,M specifically suppressed M-MuLV production in NIH 3T3/M-MuLV cells (14). M-IBDET inhibits viral synthesis by blocking the translation of viral polyprotein precursors, thus suppressing viral structural protein production (9,11). The mechanism of inhibition was shown to be at the level of mRNA translation rather than interference with viral gene transcription (10).…”