トリパノソーマ治療薬スラミンの抗ウイルス活性 : 日本脳炎ウイルス複製の阻害

抄録

Suramin, a polysulfonated naphthylurea, has been used for the treatment of trypanosomias and onchocerciasis, and is a potent inhibitor of nucleic acid polymerase including reverse transcriptase and DNA polymerase. This drug is used to examine an antiviral activity in the case of Japanese encephalitis virus (JEV) infection. Japanese encephalitis occurs in endemic and epidemic form over a wide area of Asia, at least tens of thousands of cases occur annually in East Asia. Although the vaccine against JEV is widely used, we have no antiviral drugs against JEV replication. Here we describe an antiviral activity of suramin on JEV replication in the cultured cells. In the presence of 50 μg/ml suramin, virus yields in human neuroblastoma cell line, IMR-32, reduced to 0.1% of control level. JEV growth in human hepatoma cell line, HepG2, was also inhibited, but inhibitory effect of suramin was lower than in IMR-32. The difference of inhibitory effects between host cells suggests that some host factors were involved in the process of inhibition of JEV growth. By Western blot analysis, it was clarified that expressions of JEV proteins, NS3 and E were markedly reduced by the treatment of suramin at 50-200 μg/ml. Especially the expression of E protein seems to be sensitive against suramin treatment. On the other hand, JEV-RNA level in the cells treated with suramin was not so different from control level, and in vitro JEV-RNA synthesis was also not inhibited by the addition of suramin. These results suggest that suramin inhibits virus replication through the influence to viral protein production, not to viral RNA synthesis.