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

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 QSAR_GA-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 QSAR_GA-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

KEYWORDS:

• SARS-CoV-2
• hybrid QSAR models
• molecular docking simulation
• retrosynthesis analysis

Acknowledgments

To complete this project, we have received a lot of support from my Prof. Dr. U. K. Deiters at the Institute of Physical Chemistry, Cologne University, Germany. He enthusiastically conveyed me a lot of experience and valuable knowledge in the field of theoretical calculations during my time studying at the Institute of Physical Chemistry. I sincerely thank my Prof. Dr. U. K. Deiters very much.

To complete this project, we have received all the necessary support conditions from Hoa Sen University, Viet Nam. .

Disclosure statement

No potential conflict of interest was reported by the author(s).