Native Folding Stability of the Main Protease of Coronavirus SARS-CoV-2 on a Gold Surface.

The main protease (Mpro) of coronavirus SARS-CoV-2 plays a critical role in viral processing and is one of the most promising targets for developing anti-COVID-19 therapeutics. Gold nanomaterials have shown essential roles in both virus detection and treatment; however, the molecular mechanisms behind their antiviral effects are not yet well understood. We provide computational insights into how enzyme-gold interactions may influence the catalytic activity of Mpro. We investigate the binding interactions and stability of the native structure of the protease after its adsorption onto a flat Au(001) surface through a series of molecular dynamics simulations. We examine three different adsorption modes of Mpro, bound to the gold surface via its domains I, II, and III, respectively. Our findings reveal that the structural changes in the native conformation of Mpro depend on the binding mode. However, unexpectedly, the structure of its active site and the three-dimensional mapping of crucial proteolytic residues His41 and Cys145 remain preserved. These insights enhance our understanding of the molecular behavior of viral proteins, demonstrating that gold-based nanomaterials can effectively target and capture important SARS-CoV-2 proteins, thereby promoting viral elimination. Additionally, our computational insights indicate that strong physical adsorption of key viral proteases onto inorganic surfaces does not necessarily lead to the distortion or unfolding of their native structures, which are essential for maintaining their biological activity.