Abstract
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.