On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2

Carolina Corrêa Giron; Aatto Laaksonen; Fernando L. Barroso da Silva

To refine this analysis at the sequence level, the PROCEEDpKa method 27 was employed to determine the EE of the RBD proteins for the most relevant studied complexes. Three questions should be addressed here: 1) if SARS-CoV-1 and 2 S RBD proteins share a common binding region when they bind to ACE2; 2) if these viral RBD proteins interact with the mAbs using a similar epitope-paratope interface; 3) if the interaction with CR3022 and CR3022' involves the same EE. The data to answer such questions is given in Figures 9 and 10 . The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.05.026377 doi: bioRxiv preprint In Figure 9 , the primary sequences of SARS-CoV-1 and 2 S RBD proteins are plotted together with the estimated ionizable amino acids of the interface with ACE2 and the antigenic regions as defined by the PROCEEDpKa method. By the different distribution of amino acids identified as EE (shown in blue), it can be seen that the electrostatic method is sensitive to the structures and their titratable groups that can produce electrical perturbations on their partners when they are interacting as demonstrated before. 27 The patterns observed for both viral SARS proteins are similar (i.e. they share a common region when they bind to ACE2) although some interesting observations can be made. Comparing the number of ionizable residues involved in the interactions for the RBD proteins of SARS-CoV-1 and ACE2 with the pair SARS-CoV-2 S RBD-ACE2, we can see an increase from 30 to 40 with a high number of common cases (22 amino acids) where the same amino acid interacts with ACE2 for both viral proteins. Most of the differences are observed for neighbor groups (e.g. "AWERKKISN" for SARS-CoV-1 and "AWNRKRISN" for SARS-CoV-2) indicating that the same biological interface was explored by the two viral RBD proteins in spite of their structural differences. The RBD protein responsible for COVID-19 clearly has more titratable residues interacting with ACE2 than its precursor. This observation suggests that its binding to ACE2 might be less specific than what happens for SARS-CoV-1. As such, the presence of an Ab may not completely block the SARS-CoV-2 S RBD-ACE2 interaction. In general, as seen in this Figure The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.05.026377 doi: bioRxiv preprint common cases is 12 while some regions are more affected by their structural differences (e.g.