Functionalized carbon nanotubes as an alternative to traditional anti-HIV-1 protease inhibitors: An understanding towards Nano-medicine development through MD simulations.

The Human Immunodeficiency Virus (HIV) has been the source of epidemic infection of AIDS for a longer period. One of the most difficult tasks is identifying novel medications that can help to decrease or control this global health hazard by overcoming drug resistance. In recent decades' nanoparticles are emerging as extremely relevant in drug delivery platforms. In the current study, the pristine (SWCNT) and hydroxyl functionalized (SWCNT-OH) versions of the SWCNT were investigated as inhibitors against the wild-type (WT) and three key mutants of HIV-1 protease (HIV-pr) (I50V, V82A, and I84V). Molecular docking of SWCNT in the catalytic domain and running all-atom MD simulations of all complexes are also part of this project. A thorough inspection of conformational dynamics from 50 ns trajectories reveals that both the pristine and SWCNT-OH can fit right to the pocket region of HIV-pr and govern flap dynamics. The binding affinity of the four HIV-pr-SWCNT/SWCNT-OH complexes was further investigated using MM-PBSA-dependent binding free energy studies. In most mutants and WT systems, SWCNT-OH was reported to bind proportionately many folds (kcal/mol) more than pristine SWCNTs. Hence, SWCNTs are possible HIV-pr inhibitors in terms of their stable existence in the pocket area, stronger binding to the protease, and regulation of flap dynamics in controlling the active site volume, which have vast potential for applications against drug resistance.