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

Xiaoqiang Huang; Robin Pearce; Yang Zhang

We designed a series of peptide binders that showed enhanced binding affinity to the SARS-CoV-2 RBD in computational experiments. Structural bioinformatics and sequence logo analyses indicated that the good binders to a high extent recapitulated the critical residues that contributed significantly to binding. Detailed inspection confirmed this point and also revealed that some extra favorable interactions were introduced to enhance binding in the top designed binders. Moreover, the designs were predicted to maintain the secondary structure of the motif, which was important for facilitating the protein-peptide binding interaction. Although our experimental results are not available yet, we would like to share these useful data to the community so that people can work together to test them, which should help to develop new antiviral drugs to combat COVID-19.