A novel inhibitor of respiratory syncytial virus isolated from ethnobotanicals

A novel low molecular weight compound, CJ 4-16-4, isolated from ethnobotanicals using bioassay-guided fractionation, was found to be a potent inhibitor of respiratory syncytial virus (RSV) in vitro and in vivo. In vitro, a very low micromolar efficacious dose was obtained against at least four of subtype A (RSV-Long, RSV A2, and RSV A6 57754) and one of subtype B (Washington) RSV strains without seeing any significant cytotoxicity to Hep-2, MDCK or Vero cell lines. The drug inhibits growth of RSV in Hep-2 cells maintained in tissue culture at a very low concentration (similar to 0.07 mu M) with cell toxicity > 400 mu M (TI > 5880). In a cotton rat model of RSV infection, the drug was able to reduce viral titers by similar to 1 log at dose 12.5 and 25 mg/kg/day, and by > 2 log at 100mg/kg/day. This antiviral activity was specific as influenza A and B and herpes simplex I and 2 viruses were not inhibited. The results obtained indicate that CJ 4-16-4 warrants clinical development. (c) 2005 Elsevier B.V. All rights reserved.