How Does the Novel Coronavirus Interact with the Human ACE2 Enzyme? A Thermodynamic Answer

The SARS-CoV-2 coronavirus pandemic is certainly the most important public health concern today. Until now there are no vaccines or treatments available, despite intensive international efforts. One of the targets for new drugs is the Coronavirus Spike Protein, responsible for its binding and entry into the host cells. The Receptor Binding Domain (RBD) found at the Spike Protein recognizes the human angiotensin-converting enzyme 2 (hACE2). The present in silico study discuss structural and thermodynamic aspects of the protein complexes involving the RBD’s from the 2002 SARS-CoV and 2019 SARS-CoV-2 with the hACE2. Molecular docking and molecular dynamics simulations of the complexes and isolated proteins were performed, providing insights on their detailed pattern of interactions, and estimating the free energy of binding. The obtained results support previous studies indicating that the chemical affinity of the new SARS-CoV-2 for the hACE2 enzyme virus is much higher than the 2002 SARS-CoV. The herein calculated Gibbs free energy of binding to the hACE2 enzyme is, depending on the technique, from 5.11 kcal/mol to 8.39 kcal/mol more negative in the case of the new coronavirus’ RBD. In addition, within each employed technique, this free energy is consistently 61±2% stronger for SARS-CoV-2 than for SARS-CoV. This work presents a chemical reason for the difficulty in treating the SARS-CoV-2 virus using drugs targeting its Spike Protein, as well as helps to explain its infectivity, while defining a minimum free energy of binding for new drugs to be designed against this disease.