SARS-CoV-2 and SARS-CoV Spike-RBD Structure and Receptor Binding Comparison and Potential Implications on Neutralizing Antibody and Vaccine Development

Abstract

SARS-CoV-2 and SARS-CoV share a common human receptor ACE2. Protein-protein interaction structure modeling indicates that spike-RBD of the two viruses also has similar overall binding conformation and binding free energy to ACE2. In vitro assays using recombinant ACE2 proteins and ACE2 expressing cells confirmed the two coronaviruses' similar binding affinities to ACE2. The above studies provide experimental supporting evidences and possible explanation for the high transmissibility observed in the SARS-CoV-2 outbreak. Potent ACE2-blocking SARS-CoV neutralizing antibodies showed limited cross-binding and neutralizing activities to SARS-CoV-2. ACE2-non-blocking SARS-CoV RBD antibodies, though with weaker neutralizing activities against SARS-CoV, showed positive cross-neutralizing activities to SARS-CoV-2 with an unknown mechanism. These findings suggest a trade-off between the efficacy and spectrum for therapeutic antibodies to different coronaviruses, and hence highlight the possibilities and challenges in developing broadly protecting antibodies and vaccines against SARS-CoV-2 and its future mutants.

COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives

“…However, some are unique, including an important salt bridge that involves different amino acids in ACE2 to bind S of SARS-CoV and 2019-nCoV. These slight differences might explain the more efficient binding of S from 2019-nCoV to ACE2, but this has not been observed in other preliminary studies [61,62].…”

Virology, Epidemiology, Pathogenesis, and Control of COVID-19

“…Vaccination probably offers the best option for COVID-19 control. Epitopes, mRNA, and S protein-RBD structure-based vaccines have been widely proposed and started [81,82]. Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform has been reported, and this technical advance is helpful for vaccine development [83].…”

In Vitro Diagnostic Assays for COVID-19: Recent Advances and Emerging Trends

“…Wt.~180 kDa) that consists of two subunits, i.e., S1 and S2 [10]. S1 contains a receptor binding domain (RBD), which is responsible for recognizing and binding with the host cell receptor, i.e., angiotensin converting enzyme 2 receptor (ACE2) found in the lower respiratory tract [11]. On the other hand, S2 contains other basic elements needed for the membrane fusion.…”