Volume 14 Supplement 3

Abstracts from the 2nd International Science Symposium on HIV and Infectious Diseases (HIV SCIENCE 2014)

Open Access

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

  • Amit M Pant1Email author,
  • Rupesh V Chikhale1,
  • Sunil S Menghani1 and
  • Pramod B Khedekar1
BMC Infectious Diseases201414(Suppl 3):P18

https://doi.org/10.1186/1471-2334-14-S3-P18

Published: 27 May 2014

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.

Authors’ Affiliations

(1)
Department of Pharmaceutical Sciences, RTM Nagpur University

Copyright

© Pant et al; licensee BioMed Central Ltd. 2014

This article is published under license to 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.

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