IDENTIFICATION AND ANALYSIS OF LEAD COMPOUNDS AGAINST HIV-1 INTEGRASE ENZYME USING ADMET PREDICTION AND DOCKING ANALYSISAbstract
Acquired immune deficiency syndrome (AIDS), one of the most challenging diseases world-wide is caused by human immunodeficiency virus (HIV), member of human retrovirus family. Various therapies and treatments of HIV are provided, but these are rapidly drug resistance in recent decades. After the explosion of HIV integrase (enzyme essential for the replication of DNA virus in the host genome), pharmacoinformatic approaches have become necessary to find target proteins and potential lead compounds. In the current study, identification of novel lead compounds for the HIV-1 integrase enzyme is done using different chemometric techniques. A set of 26 compounds obtained from literature are used for the ADMET prediction using DruLiTo software. The FlexX score of the compo-unds C2 and C10, fitting all the ADMET properties, with the target protein is found to be – 8.0 and – 18.4 respectively. These ligands are further analysed for the core replacement studies using ReCore module of LeadIt software which gave two novel compounds from Zinc database qualifying the ADMET properties with FlexX score of – 10.3 for ZINC0358167 and – 12.2 for ZINC2184697 respectively. The docking score of lead compounds obtained from ZINC database are compared and found to be superior to that of the FDA approved drugs Raltegravir and Elvitegravir. The analysis of binding preferences and improvement of the inhibitory potency is done.
D. Pandey*, U. Chouhan and N. Verma
Department of Mathematics, Bioinformatics and Computer Applications, Maulana Azad National Institute of Technology, Bhopal, Madhya Pradesh, India.
10 March, 2017
23 May, 2017
27 May, 2017
01 October, 2017