Multi-Scale Computational Study on SARS-CoV and SARS-CoV-2

The ongoing outbreak of COVID-19 has been a serious threat to human health worldwide. The virus SARS-CoV-2 initiates its infection to the human body via the interaction process of its spike (S) protein with the human Angiotensin-Converting Enzyme 2 (ACE2). Therefore, understanding the fundamental mechanisms of how S protein receptor binding domain (RBD) binds to ACE2 is essential for new treatments developments of COVID-19. Here we implemented multi-scale computational approaches to study the binding mechanisms of binding between ACE2 and S proteins of both SARS-CoV-2 and SARS-CoV. Electrostatic features of SARS-CoV and SARS-CoV-2 were calculated and compared. The results demonstrate that SARS-CoV and SARS-CoV-2 S proteins are both attractive to ACE2 by electrostatic forces even at difference distances. However, the residues contributing to the electrostatic features are quite different due to the mutations between SARS-CoV S protein and SARS-CoV-2 S protein. Key residues that are involved in salt bridges and hydrogen bonds are identified in this study, which may help the future drug design against COVID-19.