How Molecular Modelling Could help in the COVID19 Crisis

SARS-CoV-2, since emerged in Wuhan, China, has been a major concern due to its high infection rate; leaving more than three million infected people around the world. Many studies endeavored to reveal the structure of the SARS-CoV-2 compared to the SARS-CoV, in order to find solutions to suppress this high infection rate. Some of these studies showed that the mutations in the SARS-CoV spike (S) protein might be responsible for its higher affinity to the ACE2 human cell receptor. In this work, we used molecular dynamic simulations and Monte Carlo sampling to compare the binding affinities of the S proteins of SARS-CoV and SARS-CoV-2 to the ACE2. Our results show that the protein surface of the ACE2 at the receptor binding domain (RBD) exhibits negative electrostatic potential, while a positive potential is observed for the S proteins of SARS-CoV/SARS-CoV-2. In addition, the binding energies at the interface is slightly higher for SARS-CoV-2 due to enhanced electrostatic interactions. The major contributions to the electrostatic binding energies result from the salt-bridges forming between R426 and ACE-2-E329 in the case of SARS-CoV and K417 and ACE2-D30 in the SARS-CoV-2. In addition, our results indicate that the enhancement in the binding energy is not due to each single mutant, but rather because of the sophisticated structural changes induced by all these mutations together. This finding suggests that it is implausible for the SARS-CoV-2 to be a lab engineered virus.