Why does the novel Coronavirus Spike Protein interact so strongly with the human ACE2? A thermodynamic answer.

de Andrade, Jones; Bruno Gonçalves, Paulo Fernando; Netz, Paulo Augusto

The SARS-CoV-2 pandemic is the biggest health concern today, but until now there are no treatments. One possible drug target is the Receptor Binding Domain (RBD) from the Coronavirus' Spike Protein, which recognizes the human angiotensin-converting enzyme 2 (hACE2). Our in silico study discusses crucial structural and thermodynamic aspects of the interactions involving RBDs from the SARS-CoV and SARS-CoV-2 with the hACE2. Molecular docking and molecular dynamics simulations explained why the chemical affinity of the new SARS-CoV-2 for hACE2 is much higher than in the case of SARS-CoV, revealing an intricate pattern of hydrogen bonds and hydrophobic interactions and estimating a free energy of binding, consistently much more negative in the case of SARS-CoV-2. This work presents a chemical reason for the difficulty in treating the SARS-CoV-2 virus using drugs targeting its Spike Protein and helps to explain its infectiousness.