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

Chunyun Sun; Long Chen; Ji Yang; Chunxia Luo; Yanjing Zhang; Jing Li; Jiahui Yang; Jie Zhang; Liangzhi Xie

The prominent sequence differences between the crucial RBMs of SARS-CoV-2 and SARS-CoV raise a critical question of whether the binding affinity of SARS-CoV-2 spike protein to human ACE2 is comparable to that of SARS-CoV. A recent study by computational modeling suggested that SARS-CoV-2 has a lower binding affinity to human ACE2, as a result of the loss of one hydrogen bond interactions 18 . However, another publication using structure analysis suggested similar binding affinities to SARS-CoV 9 . By using biolayer interferometry binding assay, Tian et al. 9 measured the SARS-CoV-2 RBD's binding affinity to human ACE2 protein to be 15.2 nM, which is comparable to previously published affinity data for SARS-CoV spike protein 19 . The above comparison of spike proteins' binding affinities to human ACE2 between SARS-CoV-2 and SARS-CoV were inconclusive or indirect, hence, a direct head-to-head comparison is desired for the understanding of the infectivity and transmissibility of SARS-CoV-2 virus.