Pentoxifylline inhibits replication of Japanese encephalitis virus: a comparative study with ribavirin

Several investigations have shown that pentoxifylline possesses broad-spectrum antiviral activity against a range of RNA and DNA viruses. However, its ability to inhibit Japanese encephalitis virus (JEV) replication has not yet been studied. The present study was designed to investigate the antiviral activity of pentoxifylline against JEV in vitro and in vivo. The activity of pentoxifylline against JEV was evaluated in vitro using cytopathic effect inhibition and plaque reduction assays. Pentoxifylline was able to inhibit JEV replication in a dose-dependent manner at a 50% inhibitory concentration (IC(50)) of 50.3 μg/mL (0.00018 μM) and a therapeutic index (TI) of 10. Experiments to study the mechanism of antiviral action of pentoxifylline using in vitro translation of viral mRNA suggested that the drug did not interfere either with early or late protein synthesis but most likely exerted its action on virus assembly and/or release. Furthermore, the in vivo study showed that pentoxifylline at a concentration of 100 mg/kg and 200 mg/kg body weight was able to protect completely mice challenged with 50 × 50% lethal dose (LD(50)) of JEV.