The unique interactions and binding/unbinding process between SARS-CoV-2 and receptor ACE2

ABSTRACT

After the first large-scale outbreak of pneumonia (COVID-19) caused by novel coronavirus (SARS-CoV-2) infection in December 2019, it was declared a global pandemic by the World Health Organization in March 2020. Significant infectivity and lethality rate pose a huge threat to the life and safety of all mankind, and we urgently need to grasp the infection/transmission behavior of the virus at the molecular level. Novel coronavirus and the 2003 outbreak of severe acute respiratory syndrome coronavirus (SARS-CoV) belong to bat SARS-like coronavirus (SARSR-COV) species, and their surface spike glycoproteins are highly homologous. The key step of their invasion into human cells is the binding of the receptor binding domain (RBD) part of the surface spike protein and human angiotensin converting enzyme 2(ACE2). Many experimental studies have reported that SARS-CoV-2 possesses a stronger binding ability than SARS-CoV. In order to explain the experimental results, molecular dynamics simulations, steered molecular dynamics simulations and umbrella sampling were performed on the binding of wild-type RBD (RBDWT) of the two viruses and ACE2. The results showed that different behaviors of the β-loop region lead to differences in key residues and interactions, and further result in differences in binding/unbinding mechanisms. The binding affinity of SARS-COV-2RBD and ACE2 is nearly 30 times that of SARS-COV-RBD. © 2022. All rights reserved.