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

Xiaoqiang Huang; Robin Pearce; Yang Zhang

Several experimental SARS-CoV-2 RBD/hACE2 complex structures have been reported [20] [21] [22] , and deposited in the Protein Data Bank (PDB) 23 . Specifically, PDB ID 6m17 is a 2.9 Ã… structure of the SARS-CoV-2 RBD/ACE2-B0AT1 complex determined using the cryogenic electron microscopy (Cryo-EM) technique 22 . Furthermore, PDB ID 6m0j is a 2.45 Ã… X-ray crystal structure of SRRS-CoV-2 RBD/hACE2 20 , while 6vw1 is a 2.68 Ã… X-ray structure of SARS-CoV-2 chimeric RBD/hACE2 21 , where the chimeric RBD is comprised of the receptor binding motif (RBM) from SARS-CoV-2 S and the core from SARS-CoV, with the mutation N439R. The three experimental complex structures are quite similar to each other in terms of global folds ( Figure 1A ). Since 6vw1 does not contain the wild-type SARS-CoV-2 RBD, we did not use it as template. Based on a preliminary examination, we found that structure quality of 6m0j was better than 6m17 (see Results and Discussion), and therefore we only considered 6m0j as the template complex.