2. Academic Validation
  3. The inhibition process of HIV-1 integrase by diketoacids molecules: Understanding the factors governing the better efficiency of dolutegravir

The inhibition process of HIV-1 integrase by diketoacids molecules: Understanding the factors governing the better efficiency of dolutegravir

  • Biochem Biophys Res Commun. 2017 Jul 1;488(3):433-438. doi: 10.1016/j.bbrc.2017.05.001.
Léa El Khoury 1,  Jean-Philip Piquemal 2,  Serge Fermandjian 3,  Richard G Maroun 4,  Nohad Gresh 5,  Zeina Hobaika 6
Affiliations

Affiliations

  • 1 UR EGP, Centre d'Analyses et de Recherche, Faculté des Sciences, Université Saint-Joseph de Beyrouth, B.P. 11-514 Riad El Solh, Beirut 1107 2050, Lebanon; Laboratoire de Chimie Théorique, UMR7616 CNRS, UPMC, Sorbonne Universités, Paris 75005, France. Electronic address: [email protected].
  • 2 Laboratoire de Chimie Théorique, UMR7616 CNRS, UPMC, Sorbonne Universités, Paris 75005, France; Institut Universitaire de France, Paris Cedex 05, 75231, France; Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, United States. Electronic address: [email protected].
  • 3 Chemistry and Biology Nucleo(S)Tides and Immunology for Therapy (CBNIT), UMR 8601 CNRS, UFR Biomédicale, Paris, France. Electronic address: [email protected].
  • 4 UR EGP, Centre d'Analyses et de Recherche, Faculté des Sciences, Université Saint-Joseph de Beyrouth, B.P. 11-514 Riad El Solh, Beirut 1107 2050, Lebanon. Electronic address: [email protected].
  • 5 Laboratoire de Chimie Théorique, UMR7616 CNRS, UPMC, Sorbonne Universités, Paris 75005, France. Electronic address: [email protected].
  • 6 UR EGP, Centre d'Analyses et de Recherche, Faculté des Sciences, Université Saint-Joseph de Beyrouth, B.P. 11-514 Riad El Solh, Beirut 1107 2050, Lebanon. Electronic address: [email protected].
PMID: 28478035 DOI: 10.1016/j.bbrc.2017.05.001
Abstract

The Human Immunodeficiency Virus-1 integrase is responsible for the covalent insertion of a newly synthesized double-stranded viral DNA into the host cells, and is an emerging target for antivirus drug design. Raltegravir (RAL) and elvitegravir (EVG) are the first two integrase strand transfer inhibitors used in therapy. However, treated patients eventually develop detrimental resistance mutations. By contrast, a recently approved drug, dolutegravir (DTG), presents a high barrier to resistance. This study aims to understand the increased efficiency of DTG upon focusing on its interaction properties with viral DNA. The results showed DTG to be involved in more extended interactions with viral DNA than EVG. Such interactions involve the halobenzene and scaffold of DTG and EVG and bases 5'G-43', 3'A35'and 3'C45'.

Keywords

Dolutegravir; Elvitegravir; Human Immunodeficiency Virus-1; Integrase strand transfer inhibitors; Viral DNA.

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