A fundamental issue related to
therapy of HIV-1
infection is the emergence of viral mutations which severely limits the long term efficiency of the
HIV-protease (HIV-PR) inhibitors. Development of new drugs is therefore continuously needed. Chemoinformatics enables to design and discover novel molecules analogous to established drugs using computational tools and databases.
Saquinavir, an anti-
HIV Protease drug is administered for HIV
therapy. In this work chemoinformatics tools were used to design structural analogs of
Saquinavir as
ligand and molecular dockings at AutoDock were performed to identify potential HIV-PR inhibitors. The analogs S1 and S2 when docked with HIV-PR had binding energies of -4.08 and -3.07 kcal/mol respectively which were similar to that for
Saquinavir. The molecular docking studies revealed that the changes at N2 of
Saquinavir to obtain newly designed analogs S1 (having N2 benzoyl group at N1) and S2 (having 3-oxo-3phenyl propanyl group at N2) were able to dock with HIV-PR with similar affinity as that of
Saquinavir. Docking studies and computationally derived pharmacodynamic and pharmacokinetic properties׳ comparisons at ACD/I-lab establish that analog S2 has more potential to evade the problem of drug resistance mutation against HIV-1 PR subtype-A. S2 can be further developed and tested clinically as a real alternative
drug for HIV-1 PR across the clades in future.