Mechanistic Insights to the Binding of Antibody CR3022 Against RBD from SARS-CoV and HCoV-19/SARS-CoV-2: A Computational Study.

Abstract

In this study, molecular dynamics (MD) simulation combined with MM/PBSA and CAS methods were performed to investigate the mechanism of binding of CR3022 against SARS-CoVRBD and HCoV-19-RBD in order to determine their holographic dynamic information. It was found that the CR3022-SARS-CoV-RBD complex was more stable during 100ns MD run than that of the CR3022-HCoV-19-RBD system. There were common conservative amino acids on the β2 sheet of RBD, including Tyr369, Phe377, Lys378, Tyr380, Gly381, Lys386, Leu390 and others. These conservative amino acids play significant roles in the binding process of CR3022 antibody against SARS-CoV-RBD and HCoV-19-RBD. It was also found that the binding mode of CR3022 to its native target SARS-CoV-RBD is more comprehensive and uniform. Moreover, the β2 sheet residue Thr385 and non-β2 sheet residues Arg408 and Asp428 of the CR3022-SARS-CoV-RBD system were found to be crucial for their binding affinities, thus forming a special conformational epitope. However, these key amino acids are not present in the CR3022-HCoV-19-RBD system. The binding mode of CR3022 and HCoV-19-RBD is similar to that of SARS-CoV-RBD, but the deficiency of crucial hydrogen-bonds and salt-bridges. Therefore, the binding of CR3022 and HCoV-19-RBD only draws on the partial mode of the binding of CR3022 and SARS-CoV-RBD, so there is a loss of affinity. Thus, in order to better fight the epidemic of COVID-19 with the CR3022 antibody, this antibody needs to further improve the neutralization efficiency of HCoV-19 through mutation of it's CDR region.