Combination of N-methylisatin-ß-thiosemicarbazone derivative (SCH16) with ribavirin and mycophenolic acid potentiates the antiviral activity of SCH16 against Japanese encephalitis virus in vitro

Aim: To investigate the drug to drug interaction of N-methylisatin-beta-thiosemicarbazone (MIBT) derivative (SCH16) with ribavirin, mycophenolic acid and pentoxifylline against Japanese encephalitis virus in vitro. Our earlier studies have reported significant antiviral activity of these compounds against Japanese encephalitis virus in vitro and in vivo. Methods and Results: An in vitro drug to drug combination analysis was carried out to investigate whether or not the direct antiviral effect shown by the individual MIBT derivative could be effectively increased when lower concentrations of two compounds in combination were used. The results of this study showed that the combination of MIBT derivative (SCH16) with ribavirin or mycophenolic acid significantly enhanced the antiviral activity of SCH16 against JEV in vitro. In contrast, the combination of SCH16 and pentoxifylline resulted in antagonism. Conclusion: The antiviral activity showed by SCH16 was enhanced in the presence of ribavirin and mycophenolic Acid. Significance and Impact of the Study: Studying the synergistic/additive interaction of the compounds in combination would help in lowering the effective concentration so as to overcome the concern of toxicity.