Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection in infants and young children, and is also a significant threat to other populations including the immunosuppressed, the elderly and those with chronic chest or cardiac disease. To expand the scope of available antiviral drugs, presently limited to ribavirin, a variety of different structural formats have been explored in the past half-dozen years. Interesting leads for future discovery and lead development include a group of biphenyl relatives (represented by CL-387626) that bind the RSV fusion (F) protein; 2-5A-antisense oligonucleotides that target the RSV genomic RNA; Rho A-derived peptides that block Rho A GTPase interaction with RSV fusion (F) protein; and several compounds of presently unknown mechanisms of action, such as benzodithiins.

01 Apr 1998·Antiviral ResearchQ2 · MEDICINE

CL387626 exhibits marked and unusual antiviral activity against respiratory syncytial virus in tissue culture and in cotton rats

Q2 · MEDICINE

Article

Author: Brian E Gilbert ; Wei-Dong Ding ; Donna K Moore-Poveda ; Boris Mitsner ; Bryan O’Hara ; Philip R Wyde

CL387626 (4,4'-Bis[4,6-di[3-aminophenyl-N,N-bis(2-carbamoylethyl)-sulfon ilimino]-1,3,5-triazine-2-ylamino-bi-phenyl-2,2'-disulfonic acid, disodium salt), a compound synthesized by Wyeth-Ayerst Research Laboratories, was tested for its cytotoxicity and antiviral activity against respiratory syncytial virus (RSV) in tissue culture and in cotton rats. The median cell inhibitory (IC50) and median efficacious (EC50) concentrations of CL387626 against RSV in proliferating HEp2 or Vero tissue culture cells were determined to be 375 and 0.25 microg/ml, respectively, giving the compound an apparent selective index (S.I.) of 1500. This compound also exhibited uncommon antiviral activity against RSV in cotton rats. In multiple experiments, a single 30 mg/kg dose of CL387626 administered intranasally 4 or 5 days prior to virus challenge, significantly inhibited pulmonary replication of RSV compared to that seen in control animals inoculated similarly with placebo (i.e. water). In contrast to these results, most lots of CL387626 failed to significantly inhibit pulmonary RSV replication when administered utilizing therapeutic administration schedules. Although some cytotoxicity was noted in tissue culture assays, no overt toxic effects were noted in any test animal, including those inoculated with > 300 mg CL387626/kg, a dose approximately 150 times the apparent minimal efficacious dose (i.e. 1.9 mg/kg).

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Indication	Highest Phase	Country/Location	Organization	Date
Respiratory Syncytial Virus Infections	Preclinical	US	Wyeth AB	-

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