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Comparing Inhibiting Activity of HIV-1 Protease between Indinavir and its Modifications Using Computational Approaches


  • Department of Biotechnology, University Institute of Engineering & Technology, Kurukshetra University, Kurukshetra, Haryana, 136119, India


Objectives: To develop a potent anti-HIV agent

Methods: In the present study, two candidate ligand compounds-Pridyl methyl piperazine with acetamide and Urea derivative were designed using Chemsketch, by replacing –OH group based on indinavir as reference molecule. Designed ligands were tested in silico individually with HIV-1 protease enzymes. Rigid docking approach was applied to both the compounds by using Autodock, and qualitative inspection of the results was carried out.

Findings: Compound Modified 2 containing functional group pyridyl methyl piperazine with acetamide in place of hydroxyl group, and compound Modified 1 having urea derivative in place of hydroxyl group has shown potential bindings with HIV-1 protease enzyme. The Modified 2 showed better interactions in rigid docking method with an average lowest binding energy of -3.87 kcal/mol towards HIV-1 protease enzyme as compared to Indinavir which showed -3.52 kcal/mol lowest binding energy. However, the Modified 1’ interactions were weak with an average lowest binding energy of +0.9 kcal/mol. In wake of the present work, it indicates that the compound Modified 2 which has been designed, has the tendency to interact with protease with efficient binding and emerges out as a potential candidate inhibitor of HIV-1 enzymes for further experimentation.

Application: Regardless of the drawbacks of chemical drugs such as its malignancy and lack of therapeutic effects, our study has shown that it is possible to produce more formidable potent anti-HIV agents.


Enzyme Docking, HIV-1, Protease, Chem-Sketch, Indinavir, Computational Approaches, Inhibiting Activity.

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