A targeted covalent small molecule inhibitor of HIV-1 fusion

Abstract

We describe a low molecular weight covalent inhibitor targeting a conserved lysine residue within the hydrophobic pocket of HIV-1 glycoprotein-41. The inhibitor bound selectively to the hydrophobic pocket and exhibited an order of magnitude enhancement of anti-fusion activity against HIV-1 compared to its non-covalent counterpart. The findings represent a significant advance in the quest to obtain non-peptide fusion inhibitors.