Orally Active Fusion Inhibitor of Respiratory Syncytial Virus

Academic Article

Abstract

  • BMS-433771 was found to be a potent inhibitor of respiratory syncytial virus (RSV) replication in vitro. It exhibited excellent potency against multiple laboratory and clinical isolates of both group A and B viruses, with an average 50% effective concentration of 20 nM. Mechanism-of-action studies demonstrated that BMS-433771 inhibits the fusion of lipid membranes during both the early virus entry stage and late-stage syncytium formation. After isolation of resistant viruses, resistance was mapped to a series of single amino acid mutations in the F1 subunit of the fusion protein. Upon oral administration, BMS-433771 was able to reduce viral titers in the lungs of mice infected with RSV. This new class of orally active RSV fusion inhibitors offers potential for clinical development.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Cianci C; Yu KL; Combrink K; Sin N; Pearce B; Wang A; Civiello R; Voss S; Luo G; Kadow K
  • Start Page

  • 413
  • End Page

  • 422
  • Volume

  • 48
  • Issue

  • 2