Bis-tetrahydrofuran: a privileged ligand for darunavir and a new generation of HIV protease inhibitors that combat drug resistance

Two inhibitors that incorporate bis-THF as an effective high-affinity P-2 ligand for the HIV-1 protease substrate binding site maintain impressive potency against mutant strains resistant to currently approved protease inhibitors. Crystallographic structures of protein-ligand complexes help to explain the superior antiviral property of these inhibitors and their potency against a wide spectrum of HIV-1 strains.