Replication inhibitors of respiratory syncytial virus
Lower respiratory infection is one of the leading causes of human death worldwide, and is the most important cause of mortality in infants. Among the pathogens responsible for these infections, human respiratory syncytial virus (RSV) accounts for approximately 20% of all respiratory infections in infants. To modulate transcription and replication, RSV uses a helical nucleocapsid containing the nucleoprotein N bound to genomic RNA, the polymerase cofactor P, the viral polymerase L and M2-1 matrix protein.
In this project, we have identified novel molecules that interfere with the binding of N to P, HEVS 77 and HEVS 78. These peptides are derived from the phosphoprotein P and inhibit viral replication in Hep2 cells with EC50 values of 60 and 15 µM, respectively. While HEVS 77 shows no cytotoxicity, HEVS 78 is cytotoxic at 100 µM. Further work is currently in progress to improve the selectivity and potency of these molecules.