RSV604 is a novel inhibitor of respiratory syncytial virus replication(EC50=0.86 uM); a putative RSV nucleoprotein(N) inhibitor in phase 2 clinical trials. IC50 value: 0.86 uM(EC50) [1] Target: RSV inhibitor RSV604, a novel benzodiazepine with submicromolar anti-RSV activity. It proved to be equipotent against all clinical isolates tested of both the A and B subtypes of the virus. The compound has a low rate of in vitro resistance development. Sequencing revealed that the resistant virus had mutations within the nucleocapsid protein. This is a novel mechanism of action for anti-RSV compounds. In a three-dimensional human airway epithelial cell model, RSV604 was able to pass from the basolateral side of the epithelium effectively to inhibit virus replication after mucosal inoculation. RSV604, which is currently in phase II clinical trials, represents the first in a new class of RSV inhibitors and may have significant potential for the effective treatment of RSV disease.

• [1]. Henderson EA, et al. 1,4-benzodiazepines as inhibitors of respiratory syncytial virus. The identification of a clinical candidate. J Med Chem. 2007 Apr 5;50(7):1685-92.

  [2]. Chapman J, et al. RSV604, a novel inhibitor of respiratory syncytial virus replication. Antimicrob Agents Chemother. 2007 Sep;51(9):3346-53.

  [3]. Challa S, et al. Mechanism of action for respiratory syncytial virus inhibitor RSV604. Antimicrob Agents Chemother. 2015 Feb;59(2):1080-7.