Structural Decoding of a Small Molecular Inhibitor on the Binding of SARS-CoV-2 to the ACE 2 Receptor

Mishra, Pushpendra Mani; Nandi, Chayan Kanti

[Image: see text] Inhibition of the interaction of the receptor-binding domain (RBD) of the spike protein and the human angiotensin-converting enzyme 2 (ACE 2) receptor is the most effective therapeutic formulation to restrict the contagious respiratory illness and multiple organ failure caused by the novel SARS-CoV-2 virus. Based on the structural decoding of the RBD of the spike protein, here we have generated a new set of small molecules that have strong inhibiting properties on the binding of the spike protein to ACE 2 receptors. These small-molecule inhibitors surprisingly show binding to the main protease, nucleoprotein, and RNA-dependent RNA polymerase, which are the other responsible factors for the viral infection. The newly designed molecules show better performance than several existing repurposed drugs. Conformational changes from closed to closed lock and open conformations of the SARS-CoV-2 binding to the ACE 2 receptor were observed in the presence of these small molecular inhibitors, suggesting their strong abilities to counteract the SARS-CoV-2 infection.