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In silico analysis of cytotoxicity, rate of absorption and molecular docking of natural products against protease, integrase and HIV-1 reverse transcriptase
* 1, 2 , 3 , 3 , 3, 4
1  Postgraduate Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, Castelo Branco - João Pessoa - Brazil.
2  Postgraduate Program in Chemistry - Federal Rural University of Pernambuco - UFRPE - Recife - PE.
3  Federal University of Paraíba, Health Sci. Center, 50670-910, João Pessoa, PB, Brazil
4  Teaching and Research Management - University Hospital, Federal University of Paraíba, João Pessoa, PB, Brazil


AIDS is an infectious disease characterized by compromising the body's defense cells, is caused by HIV, a retrovirus that affects 36.90 million people worldwide, its main means of transmission is unprotected sexual intercourse. In its viral multiplication process, HIV requires protease, integrase and reverse transcriptase which are important enzymes in the process. Many therapeutic alternatives in the anti-HIV treatment are in the inhibition of these enzymes, in the attempt to close the process of viral multiplication. The use of natural products in anti-HIV research has been increasing. The aim of this research was to carry out chemoinformatic studies using cytotoxicity risk prediction tools; prediction of absorption and molecular docking of natural products found in the database of chemical structures (ChemBL) and literature. Thus it was possible to evaluate the interactions with the targets, also the analysis of some pharmacokinetic and cytotoxicological properties important for the study. We used 243 natural products and 18 drugs already used in anti-HIV treatment. All molecules had their 3D structures optimized by the methods of mechanical molecules (MM +) and Semi-empirical methods (AM1) (RMS 0.1 kcal / Å.mol in 600 cycles) through HyperChemTM 8.0 software. Structures were imported into the software OSIRIS DataWarrior 4.3.7 for prediction of cytotoxicity risks and absorption rate was calculated based on TPSA. Finally, molecular docking was performed using the software Molegro Virtual Docker 6.0 to calculate the energies of interaction with the protease receptors (PDB ID: 1OHR; reverse transcriptase PDB ID: 1REV and integrase (PDB ID: 3WNH). Of the 243 molecules of natural products with anti-HIV activity, 29 were promising for lack of cytotoxicity (mutagenicity, carcinogenicity, skin irritability and reproductive system effect), better MolDockScore energies for all targets studied simultaneously by varying the interaction energies ligand-receptor from -192.23kJ.mol-1 to -62.74kJ.mol-1 and absorption rate (% ABS) between 42.90% and 88.06%.

Keywords: molecular docking, natural products, HIV, cytotoxicity, rate of absorption.