The emergence of drug-resistant strains used in antiretroviral therapy grows alarmingly on a
global scale. Antiretrovirals used in the treatment of first and second line HIV are the ones
that most have case reports of resistant strains. Protease inhibitors are a class of antiretroviral
drugs that play a key role in AIDS treatment regimens. In addition to the emergence of
resistance to IPs used in the usual treatment regimens, Darunavir, a protease inhibitor used in
therapeutic rescue treatment, is already reported in patients who already have failed initial
treatment and proven resistance. The aim of this work is to evaluate, identify and quantify
HIV-1 3UCB protease mutations, as well as to evaluate, through molecular dynamics
simulations, the impact that mutations produce on the interaction of 3UCB and its darunavir
ligand when compared to the native HIV-1 protease 4LL3 complexed to the same linker.The
results obtained in this study showed that the 3UCB multi-resistant HIV-1 protease had a
slightly more stable binding profile than the native HIV-1 protease complex 4LL3, with
binding free energy results -68.77 and -64.62 kcal / mol, respectively.
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