Biophysical evolution of the receptor binding domains of SARS-CoVs

Biophys J. 2023 Oct 27:S0006-3495(23)00662-8. doi: 10.1016/j.bpj.2023.10.026. Online ahead of print.ABSTRACTWith hundreds of coronaviruses (CoVs) identified in bats that can infect humans, it is essential to understand how CoVs that affected the human population have evolved. Seven known coronaviruses have infected humans, of which three CoVs caused severe disease with high mortality rates: SARS-CoV emerged in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019. SARS-CoV and SARS-CoV-2 belong to the same family, follow the same receptor pathway, and use their receptor binding domain (RBD) of spike protein to bind to the ACE2 receptor on the human epithelial cell surface. The sequence of the two RBDs is divergent, especially in the receptor binding motif (RBM) that directly interacts with ACE2. We probed the biophysical differences between the two RBDs in terms of their structure, stability, aggregation, and function. Since RBD is being explored as an antigen in protein subunit vaccines against CoVs, determining these biophysical properties will also aid in developing stable protein subunit vaccines. Our results show that despite RBDs having a similar three-dimensional structure, they differ in their thermodynamic stability. RBD of SARS-CoV-2 is significantly less stable than that of SARS-CoV. Correspondingly, SARS-CoV-2 RBD shows a higher aggregation propensity. Regarding binding to ACE2, less stable SARS-CoV-2 RBD binds with a higher affinity than more stable SARS-CoV RBD. In add...

Source: Biophysical Journal - October 28, 2023 Category: Physics Authors: Vaibhav Upadhyay Sudipta Panja Alexandra Lucas Casey Patrick Krishna M G Mallela Source Type: research