Irin Sarah Jacob, Archana Singh, Sarika N Suryawanshi, Vikas Gautam
Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER) EPIP Campus, Industrial Area, Hajipur – 844102, Bihar, India.


Acquired immune deficiency syndrome (AIDS) is a disease of the human immune system caused by the human immunodeficiency virus (HIV). The illness interferes with the immune system making peoples with AIDS much more likely to get infections and tumours that do not affect people with working immune systems. This susceptibility gets worse as the disease progresses. In 2009, the World Health Organization (WHO) estimated that there are 33.4 million people worldwide living with HIV/AIDS, with 2.7 million new HIV infections per year and 2.0 million annual deaths due to AIDS. HIV integrase is one of the three enzymes encoded in the HIV genome. It mediates the retroviral process of integration-insertion of the proviral DNA into that of the host cell. HIV integrase acts minimally as a pair of homodimers and catalyses two reactions 3′-processing, where two bases are removed from the blunt-ended proviral DNA and strand transfer, where each end of the proviral DNA is covalently bonded to the host DNA. The essential nature of integrase in HIV replication makes it a prime target for anti- HIV drug discovery. Structural characterisation of the 3D structure of HIV integrase that we got from protein databank shows that the structure was crystallized with sucrose at a high resolution of 1.4 A which consists of two chains A and B and the active site residues shares both monomeric units.Our methodology for finding the novel inhibitors against HIV integrase included the protein preparation of the 3D structure using the Protein Preparation Wizard in Schrodinger 9.2. This step is important to stabilise, delete unwanted water molecules and minimise the 3D structure. Crystal structure shown 0.0% generously allowed and disallowed regions in Ramachandran plot through Procheck validation. Further step was the receptor grid generation, on the active site as given in the literature which provides the special docking environment to the compounds. This step was done by Glide module of Schrodinger 9.2. In the next step, compounds from the PubChem database were taken for the generation of ligand library. This library of ligands was minimised using the LigPrep and filtered through QikProp including filters like Lipinski Rule and reactive functional groups. Filtered library of compounds was then given as an input to the Virtual Screening Workflow which allows compounds interaction through HTVS, SP and XP docking respectively. Finally the top compounds with high Glide GScores were selected which suggests binding affinity against the target and may serve as potent inhibitors after assays and trials.Read more…

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