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      LEDGF/p75 IN interaction inhibitors: in silico studies of an old target with novel approach

      abstract
      1 , , 1 , 1 , 1
      BMC Infectious Diseases
      BioMed Central
      2nd International Science Symposium on HIV and Infectious Diseases (HIV SCIENCE 2014)
      30 January-1 February 2014

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          Abstract

          Background Despite development in Anti Retroviral Therapy (ART), reports of HIV infection remains in continuous momentum and a cure seems to be imaginary. Raltegravir, an Integrase (IN) inhibitor, provides some life expectancy to patients on salvage therapy. Nowadays, IN inhibitors reported with resistance and shows cross resistance to other drugs in this class. Human Lens Epithelium Derived Growth Factor (LEDGF)/p75 plays a vital role in the HIV life cycle and its importance has been shown in numerous studies. In the LEDGF/p75 IN complex, LEDGF binds to IN at a region other than the catalytic active site. Thus, we tried computationally to approach these IN-LEDGF interaction sites as a novel target in therapy. Methods The computational studies involved protein preparation, ligand preparation and energy minimization, grid generation, docking and analysis of results. A library of 396 molecules were prepared considering a pyrimidine ring as core. These operations were performed using Maestro, Discovery studio and VLife Sciences suites. Results It is known that Ile365 establishes a hydrogen bond with backbone carbonyl group of IN Gln168 whereas Asp366 of LEDGF/p75 forms a hydrogen bond with Glu170, on similar basis it was found that AMP_1071 exhibits hydrogen bonding with Gln95 of one monomer and Gln168, Hie171, and Thr174 of another monomer of IN. Conclusion The designed molecule AMP_1071 shows topological similarity to LEDGF/p75 binding surface. Further antiviral activity, pharmacokinetic and tolerability studies are ongoing. The LEDGF binding inhibitors lacks the cross resistance to any class of ART, possibly making this class as add on to highly active anti-retroviral therapy.

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          Author and article information

          Contributors
          Conference
          BMC Infect Dis
          BMC Infect. Dis
          BMC Infectious Diseases
          BioMed Central
          1471-2334
          2014
          27 May 2014
          : 14
          : Suppl 3
          : P18
          Affiliations
          [1 ]Department of Pharmaceutical Sciences, RTM Nagpur University, Nagpur, India
          Article
          1471-2334-14-S3-P18
          10.1186/1471-2334-14-S3-P18
          4080469
          a587c365-fe94-4aa7-9d68-638dec3a21e3
          Copyright © 2014 Pant et al; licensee BioMed Central Ltd.

          This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

          2nd International Science Symposium on HIV and Infectious Diseases (HIV SCIENCE 2014)
          Chennai, India
          30 January-1 February 2014
          History
          Categories
          Poster Presentation

          Infectious disease & Microbiology
          Infectious disease & Microbiology

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