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 50.3microg/mL (0.00018microM) 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 100mg/kg and 200mg/kg body weight was able to protect completely mice challenged with 50 x 50% lethal dose (LD(50)) of JEV.
Sebastian
Liba
L
Department of Neurovirology, National Institute of Mental Health and Neurosciences, Bangalore, India.
Desai
Anita
A
Madhusudana
Shampur Narayan
SN
Ravi
Vasanthapuram
V
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004664:Encephalitis Virus, Japanese / Q000187:drug effects* / Q000502:physiology; D004672:Encephalitis, Japanese / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D051379:Mice; D008826:Microbial Sensitivity Tests; D010431:Pentoxifylline / Q000494:pharmacology* / Q000627:therapeutic use*; D012254:Ribavirin / Q000494:pharmacology* / Q000627:therapeutic use*; D016019:Survival Analysis; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D012254:Ribavirin; D010431:Pentoxifylline