%0 Journal Article
%T Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D¡üG¡üS mutant in the South African HIV-1 subtype C protease
%A Eden Padayachee
%A Glenn Maguire
%A Johnson Lin
%A Kruger Hendrik Gerhardus
%A Sibusiso Maseko
%A Siyabonga Maphumulo
%A Sooraj Baijnath
%A Thavendran Govender
%A Tricia Naicker
%A Yasien Sayed
%J Journal of Enzyme Inhibition and Medicinal Chemistry
%D 2019
%R https://doi.org/10.1080/14756366.2019.1636234
%X Abstract Herein, we report the effect of nine FDA approved protease inhibitor drugs against a new HIV-1 subtype C mutant protease, E35D¡üG¡üS. The mutant has five mutations, E35D, two insertions, position 36 (G and S), and D60E. Kinetics, inhibition constants, vitality, Gibbs free binding energies are reported. The variant showed a decreased affinity for substrate and low catalytic efficiency compared to the wild type. There was a significant decrease in the binding of seven FDA approved protease inhibitors against the mutant (p£¿<£¿.0001). Amprenavir and ritonavir showed the least decrease, but still significant reduced activity in comparison to the wildtype (4 and 5 folds, respectively, p£¿=£¿.0021 and .003, respectively). Nelfinavir and atazanavir were the worst inhibitors against the variant as seen from the IC50, with values of 1401£¿¡À£¿3.0 and 685£¿¡À£¿3.0£¿nM, respectively. Thermodynamics data showed less favourable Gibbs free binding energies for the protease inhibitors to the mutant
%U https://www.tandfonline.com/doi/full/10.1080/14756366.2019.1636234