AIDS is a chronic infection that compromises the immune system of the individual infected with HIV, leaving him vulnerable to secondary infections. According to the Ministry of Health in 2017 there were 200,000 cases in Brazil, considered a worldwide pandemic with a record 36.7 million cases to date. HIV is a retrovirus, that is, it has RNA as a genetic material, and needs the action of reverse transcription (TR) to multiply. A nucleoside is formed by the N-glycosidic bond between a carbohydrate and a nitrogenous base (purine or pyrimidine) which in the biological medium is phosphorylated and inserted into the genetic material at the time of HIV viral multiplication. The bioactives analogous to the natural nucleosides upon being inserted by the TR into the DNA strand of an infected cell are not encoded and the retroviral multiplication process is immediately terminated by non-recognition of that analog. The major difficulty today is the action of these nucleoside analogs on other non-selective biological targets, such as the protease enzyme, and integrates, conferring toxicity to uninfected cells. This work consists of a computational analysis through Molecular Docking to predict the potential inhibitory activity of reverse transcriptase from a series of 24 nucleoside analogues derived from fructopyranose compared to the bioactive molecules already inserted in the anti-HIV treatment. For this study 36 molecules were designed in ChemDraw Ultra 12.0 to obtain its 2D structural formula. Then the molecule was optimized (RMS 0.1 kcal / Å.mol in maximum 660 cycles) by the Molecular Mechanics (MM +) and Semi-empirical (AM1) methods with the help of HyperChemTM (Release 8.0.6 for Windows) software for of the 3D structure. Finally, the enzyme reverse transcriptase in PBD (PDB ID 1REV) was selected and in Molegro Virtual Docking 6.0 anchorage was performed. Analyzing the results, it is possible to conclude that some molecules presented energies favorable to the formation of the ligand-enzyme complexes, as well as the presence of interactions with amino acid residues common to known inhibitors. Thus, this study contributes to obtaining new anti-HIV biomolecules through monosaccharides easily found in nature.
Molecular docking of fructose-derived nucleoside analogs against reverse transcriptase of HIV-1
Published: 10 May 2019 by MDPI AG in MOL2NET 2019, International Conference on Multidisciplinary Sciences, 5th edition session CHEMINFOUNC-01: Chemoinformatics Workshop, UNC Chape Hill, USA, 2019
Keywords: HIV, Reverse transcriptase, docking molecular, nucleoside, fructose