Application of drug design strategies to predict new bioactive molecules

Bourougaa, Lotfi (2024) Application of drug design strategies to predict new bioactive molecules. Doctoral thesis, Université Mohamed Khider (Biskra - Algérie).

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Abstract

Influenza is a pulmonary infection triggered by a virus that produces fever. Periodic epidemics can be fatal. Antiviral therapy shortens the length of sickness by around one day and will need to be explored especially for high-risk individuals. This work was focused on discovering and developing novel and effective anti-influenza medicines. Neuraminidase was chosen as the major target due to its critical activity and importance in the life of the influenza virus. Several compounds were created in the first stage using pharmacophore modeling, fragment-based drug design, Breed-Based De Novo Hybridization and 3D-QSAR (CoMFA model). The docking modeling data reveal that all of the designed compounds bind well to the Neuraminidase receptor in comparison with the clinical blockers. Moreover, each compound's pharmacokinetic profile has been verified, particularly its aqueous solubility, permeability, and bioavailability. The potential toxicity of each developed molecule was assessed using the ProTox II platform and the VEGA QSAR package. The atomic mobility of the generated complexes between the proposed compounds and Neuraminidase receptor was examined using molecular dynamics simulations performed for 100 ns via Gromacs package. All of the data show that the formed complexes (designed molecules_Neuraminidase) have high biomolecular stability. Finally, the results of molecular docking were confirmed by MM-BPSA calculations.

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