DFT, Molecular Docking, ADME, and Cardiotoxicity Studies of Persuasive Thiazoles as Potential Inhibitors of the Main Protease of SARS‐CoV‐2

Abstract

This study explores the capability of thiazoles as potent inhibitors of SARS‐CoV‐2 Mpro. Seventeen thiazoles (1‐17) were screened for their linking affinity with the active site of SARS‐CoV‐2 Mpro and compared with the FDA‐recommended antiviral drugs, Remdesivir and Baricitinib. Density Functional Theory (DFT) calculations provided electronic and energetic properties of these ligands, shedding light on their stability and reactivity. Molecular docking analysis revealed that thiazole derivatives exhibited favorable linking affinities with various functional sites of SARS‐CoV‐2 proteins, including spike receptor‐linking zone, nucleocapsid protein N‐terminal RNA linking zone, and Mpro. Notably, compounds 3, 10, and 12 displayed the best interaction with 6LZG as compared to FDA‐approved antiviral drugs Remdesivir and Baricitinib, while compounds 1, 10, and 8 exhibited strong linking with 6M3M and also better than Remdesivir and Baricitinib. Additionally, compounds 3, 1, and 6 showed promising interactions with 6LU7 but only compound 3 performed better than Baricitinib. An ADME (Absorption, Distribution, Metabolism, and Excretion) study provided insights into the pharmacokinetics and drug‐likeness of these compounds, with all ligands demonstrating good physicochemical characteristics, lipophilicity, water solubility, pharmacokinetics, drug‐likeness, and medicinal chemistry attributes. The results suggest that these selected thiazole derivatives hold promise as potential candidates for further drug development.