Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIV

Our structure-based design strategies which specifically target the HIV-1 protease backbone, resulted in a number of exceedingly potent nonpeptidyl inhibitors. One of these inhibitors, darunavir (TMC114), contains a privileged, structure-based designed high-affinity P2 ligand, 3(R)(R),3a(S)(S),6a(R)(R)-bis-tetrahydrofuranylurethane (bis-THF). Darunavir has recently been approved for the treatment of HIV/AIDS patients harboring multidrug-resistant HIV-1 variants that do not respond to previously existing HAART regimens.

This perspective article describes our structure-based design efforts targeting the protein-backbone of HIV-1 protease to combat drug- resistance. Darunavir has been recently approved for the treatment of drug- resistant HIV.Figure optionsDownload as PowerPoint slide