Inhibition of poliovirus replication by N-methylisatin-β-4′:4′-dibutylthiosemicarbazone

Abstract

Since N-methylisatin-β-4′:4′-dibutylthiosemicarbazone (busatin) has been reported to inhibit the replication of RNA viruses, we investigated its mechanism of inhibition of poliovirus synthesis in HeLa cells. It was observed that busatin inhibited the growth and DNA synthesis, but not RNA synthesis, of HeLa cells. In addition, busatin blocked poliovirus (types 1, 2, and 3) replication and viral RNA synthesis at any time in the replication cycle. Furthermore, busatin directly inhibited the cell-free, polio RNA polymerase reaction which differentiates it from other polio inhibitors such as guanidine and 2-(α-hydroxybenzyl)benzimidazole. Both the inhibition of cellular DNA synthesis and polio RNA synthesis could be reversed by washing the treated cells free of busatin. The parent compound, isatin-β-thiosemicarbazone, neither inhibited poliovirus replication nor the in vitro polymerase reaction. It is concluded that busatin blocks poliovirus replication not as a consequence of a toxic effect on HeLa cells, but by causing a discrete lesion in viral RNA synthesis.