A COMBINATORIAL APPROACH TO IDENTIFY NOVEL HIV-PROTEASE (WILD AND MUTANT) INHIBITORS (PIs) USING ZINC DRUG DATABASEAbstract
The Human immunodeficiency virus type-1 protease is one of the most important target to highly active anti retrovirus therapy(HAART) for the treatment of all acquired immune deficiency syndrome(AIDS). Protease inhibitor “Darunavir” is most recently included as a PI in the list of HARRT(highly active anti retrovirus therapy), more effective against mutant and wild type simultaneously of Protease with increased no. of H bonding then precursors approved by FDA, So herein we have taken Darunavir as a base structure for virtually identification of more/similar efficient drug like leads then Darunavir using ten different PDB structures (3EM6, 3OXW, 3BVB, 3CYW, 3D1Y, 4DQB, 4DQH, 4DQE, 4DQF, 4DQC & 3EKT) of Protease from PDB database ‘RCSB’ versus chemical compounds database ‘ZINC’ using Schrodinger and Discovery Studio software. Using molecular constraint search with similarity coefficient ‘Tanimoto’, 1,65,000 ligands were extracted and docking analysis were resulted some efficient in docking and in other computational medicinal parameters, we are reporting such lead molecules, and they may further undergo through high end extensive virtual investigation and beyond..
K.K. Srivastava, Shubha Srivastava , Tanweer Alam and Rituraj *
Department of Chemistry, Vinoba Bhave University, Hazaribagh, Jharkhand India
19 November, 2014
15 January, 2015
16 April, 2015
01 July, 2015