NOVEL SARS-CoV-2 INHIBITORS FROM PHENETHYLTHIAZOLETHIOUREA DERIVATIVES USING HYBRID QSAR MODELS AND DOCKING SIMULATION

Abstract

ABSTRACT Currently, there are several groups of HIV-1 virus inhibitors that could potentially be used in the treatment of SARS-CoV-2. Particularly, the phenethylthiazolethiourea compounds are capable of inhibiting HIV-1 RT and have been tested by IC50. This work contributed to the search for SARS-CoV-2 inhibitors; a group of these compounds was developed to obtain SARS-CoV-2 inhibitors. The hybrid QSARGA-ANN model with I(5)-HL(9)-O(1) architecture used for developing for HIV-1 inhibitors and it successfully predicted the pIC50 activities of six newly designed compounds. The predicted results of the pIC50 activity received from the QSARGA-ANN model agreed well with the docking simulation. The C-n6 new molecule that has been bound to the SARS-CoV-2 protein receptors (PDB ID: 6LU7) using docking simulation. It demonstrated a more effective activity against HIV-1 (PDB ID: 1ODW). This compound C-n6 exhibited the binding affinity for the HIV-1 protein (1ODW) is −23.6137 kJ.mol-1; for the target protein SARS-CoV-2 (6LU7), its binding affinity is −27.4235 kJ.mol-1. The retrosynthesis plan for the most active substance C-n6 1-(2-chloro-5-hydroxy-4-nitrophenethyl)-3- (thiazol-2-yl) thiourea has been successfully constructed. In this research the designed directions for new substances can generate the SARS-CoV-2 inhibitory drugs in a fast and reliable way. GRAPHICAL ABSTRACT