Discovery of N-Containing (-)-Borneol Esters as Respiratory Syncytial Virus Fusion Inhibitors.

Respiratory syncytial virus (RSV) causes acute respiratory infections, thus, posing a serious threat to the health of infants, children, and elderly people. In this study, we have discovered a series of potent RSV entry inhibitors with the (-)-borneol scaffold. The active compounds , , , , , , , and were found to exhibit activity against RSV A strain A2 in HEp-2 cells. The most active substances, (IC = 8.9 μM, SI = 111) and (IC = 5.0 μM, SI = 83), displayed more potency than the known antiviral agent Ribavirin (IC = 80.0 μM, SI = 50). Time-of-addition assay and temperature shift studies demonstrated that compounds , , and inhibited RSV entry, probably by interacting with the viral F protein that mediated membrane fusion, while they neither bound to G protein nor inhibited RSV attachment to the target cells. Appling procedures of molecular modeling and molecular dynamics, the binding mode of compounds and was proposed. Taken together, the results of this study suggest (-)-borneol esters to be promising lead compounds for developing new anti-RSV agents.