Probing Multidrug-Resistance and Protein-Ligand Interactions with Oxatricyclic Designed Ligands in HIV-1 Protease Inhibitors

摘要

The introduction of HIV-1 protease inhibitors (Pls) into highly active antiretroviral therapy (HAART) in 1996 had a critical impact in decreasing HIV-related morbidity and mortality. Indeed, HAART regimens with Pls initially suppressed HIV-1 replication in patients to undetectable HIV-1 RNA levels in plasma.l However, one of the serious shortcomings of current treatments is the rapid emergence of drug-resistant HIV strains.There is an urgent need for improved Pls for the treatment of the increasing number of treatment-experienced patients harboring multidrug-resistant HIV-1 strains.