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 (approximately 0.07 microM) with cell toxicity >400 microM (TI>5880). In a cotton rat model of RSV infection, the drug was able to reduce viral titers by approximately 1 log at dose 12.5 and 25 mg/kg/day, and by >2 log at 100 mg/kg/day. This antiviral activity was specific as influenza A and B and herpes simplex 1 and 2 viruses were not inhibited. The results obtained indicate that CJ 4-16-4 warrants clinical development.
Ojwang
Joshua O
JO
ZymeTx, Inc., Oklahoma City, OK 73104, USA. Ojwangj@zymetx.com
Wang
Yan-Hong
YH
Wyde
Philip R
PR
Fischer
Nikolaus H
NH
Schuehly
Wolfgang
W
Appleman
James R
JR
Hinds
Soreeta
S
Shimasaki
Craig D
CD
D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology*; D018929:Cell Culture Techniques; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy; D012136:Respiratory Syncytial Viruses / Q000187:drug effects*
D000998:Antiviral Agents; D004365:Drugs, Chinese Herbal; C472707:caffeoylquinic acid; D011801:Quinic Acid