In-silico study for the identification of potential destabilizers between the spike protein of SARS-CoV-2 and human...

The emergence of the new SARS-CoV-2 virus, which causes the disease known as COVID-19, has generated a pandemic that has plunged the world into a health crisis. The infection process is triggered by the direct binding of the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) of the host cell. In the present study, virtual screening techniques such as molecular docking, molecular dynamics, calculation of free energy using the GBSA method, prediction of drug similarity, pharmacokinetic, and toxicological properties of various ligands interacting with the RBD-ACE2 complex were applied. The ligands radotinib, hinokiflavone, and ginkgetin were identified as potential destabilizers of the RBD-ACE2 interaction, which could produce their pharmacological effect by interacting at an allosteric site of ACE2, with affinity energy values of -10.2 ± 0.1, -9.8 ± 0.0, and -9.4 ± 0.0 kcal/mol, indicating strong receptor affinity. The complex with hinokiflavone showed the highest conformational stability and rigidity of the dynamic simulation and also obtained the best binding free energy of the three molecules, with an energy of -215.86 kcal/mol.