Molecular docking and molecular dynamics simulation studies of thiazole-coumarin and thiazole-triazole conjugates against Mpro and ACE2 receptor for SARS COV-2.

Abstract

The recent COVID-19 pandemic, which caused severe respiratory infections and multiple organ failure leading to death, has drawn the attention of researchers around the world. Several vaccines are available for protection against SARS-CoV-2. However, the frequent changes in its viral genome have raised concerns about the efficacy of current vaccines. Most of the research has focused on developing novel therapeutic agents, and till now no approved anti-viral drugs are available. The development of an effective and approved drug is a time-consuming process, so research is increasingly focusing on the screening of highly active molecules based on computer-aided drug designs. Heterocyclic moieties like coumarin, thiazole, and triazole exhibit diverse biological applications. To identify potent inhibitors of SARS-CoV-2 targets, we performed molecular docking and dynamics simulations on thiazole-coumarin and thiazole-triazole conjugates. These compounds effectively target the viral M^pro and ACE2 receptors. Based on the results obtained, RD9, RD12, RD17, and RD18 were found to be most active. These molecules make an excellent interaction with the active site of both enzyme M^pro and ACE2 with a free binding energy of - 8.33, - 7.89, - 8.61, - 8.02, - 9.87, - 9.75, - 9.49, - 9.61 kcal mol^-1 respectively which can potentially be used as a dual inhibitor. Molecular dynamics simulation studies further confirm the stability of these complexes. These findings suggest that thiazole-coumarin and thiazole-triazole conjugates can serve as potential candidates for dual inhibition of M^pro and ACE2 enzyme, and can be effectively used to control COVID-19 infection.