Filling the hole: evidence of a small molecule binding to the fusion core pocket in human respiratory syncytial virus

Abstract

Searching for small molecules to inhibit envelope virus fusion has long been a frontier field for both academic research and the biomedical industry. Targeting the formation of trimer-of-hairpin in class I viral envelope proteins has been shown to be an effective method by using homologous peptides. Substituting the peptides by using small molecules to bind to the same target in human respiratory syncytial virus has been successfully achieved in this paper. The authors, for the first time, show that their small molecules occupy the hydrophobic cavity of the inner coiled core of the trimer-of-hairpin. Their previous studies also showed that one of them, BMS-433771, is orally active in fusion inhibition in rodent models.

• BMS-356188
• BMS-433771
• fusion core
• inner coiled core
• pocket, heptad repeat
• small molecule
• trimer-of-hairpin
• viral fusion