Computational Design of Peptides to Block Binding of the SARS-CoV-2 Spike Protein to Human ACE2

Xiaoqiang Huang; Robin Pearce; Yang Zhang

. CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.28.013607 doi: bioRxiv preprint The wild-type peptide showed an EvoEF2 binding energy of -46.3 EEU, whereas the total energy of the wild-type peptide/SARS-CoV-2 RBD complex was -802 EEU ( Figure 2D ). 757 out of the 992 designs exhibited better binding affinities to SARS-CoV-2 RBD and showed lower total energies than the wild-type, and some designs showed good binding and stability simultaneously ( Figure 2D ), indicating that the wild-type peptide could be improved through design. Figure 2E illustrates the binding energy as a function of sequence identity for the designed peptides; it illustrates that a majority of the designs showed weaker binding affinity to SARS-CoV-2 than the wild-type peptide when the sequence identity was <25%, whereas most of the designs with sequence identities >35% exhibited stronger binding to SARS-CoV-2. These results suggest that, in general, low sequence identity designs may not be as good as high sequence identity designs.