Characterisation of mutated proteinases derived from hiv-positive patients: Enzyme activity, vitality and inhibition

摘要: HIV protease (PR) specifically cleaves viral polyproteins to yield infectious progeny virus particles. Inactivation of PR leads loss infectivity and thus became an attractive pharmaceutic target. Indeed, seven inhibitors (PI) have been approved for clinical use date. However, emerging resistant variants with reduced sensitivity PIs become a major obstacle successful control replication. We previously reported the design, testing structural analysis pseudopeptide inhibitor, QF34, which efficiently inhibits wide variety variants. In study, we monitored more than 100 HIV-positive patients in Czech Republic undergoing highly active antiretroviral therapy including PI. this paper describe kinetic characterisation two species isolated from these patients. The mutated proteases accumulated as much 14 amino acid exchanges develop resistance saquinavir, ritonavir, indinavir nelfinavir vitality value up 150. Kinetic analyses revealed that second-generation PI lopinavir QF34 retained their subnanomolar potency against both multidrug These results suggest route design capable inhibiting mutants.