In silico studies of thiazole derivative towards its potential use against SARS-CoV-2: An intuition from an experimental and computational approach

Abstract

The N-(4-methoxyphenyl)-4-phenylthiazole-2-carboxamide (TT7) obtained via cyclization of methyl 2-((4-methoxyphenyl)amino)-2-oxoethanedithioate with ɑ-haloketone and then characterized by 1H-NMR and 13C-NMR spectroscopy, and single crystal X-ray diffraction method. Weak intermolecular interactions like C-H...O, C-H...π, C-O...π, and π...π interactions help to stabilize the compound TT7. The weak interactions formed in the solid structure of the compound TT7 were meticulously investigated using theoretical approach like Hirshfeld surface analysis using crystallographic information file (.cif). Further, the density functional theory calculations have been performed to obtain the optimized geometry of the structure, and to explore the electronic properties of the molecule. The charge distribution on the molecular surface is analyzed by the molecular electrostatic potential (MEP) map. QTAIM and RDG analyses were done to explore the weak interactions (intramolecular) in the compound TT7 in the gaseous phase. The compound TT7 displayed good in silico results against SARS-CoV-2 main protease. Molecular docking study on SARS-CoV-2 virus major protease (PDB IDs: 6LZE and 6LU7) shows higher docking scores. Molecular dynamics simulations confirmed the inhibitory action of the newly synthesized compound (TT7). The binding free energy and contributed energies were determined using the MM-GBSA technique. The 6LU7-ligand complex has the highest binding free energy, with considerable contributions from covalent and van der Waals interactions.