SARS-CoV-2 is coronavirus causing COVID-19 pandemic. To enter human cells, receptor binding domain of S1 subunit of SARS-CoV-2 (SARS-CoV-2-RBD) binds to peptidase domain (PD) of angiotensin-converting enzyme 2 (ACE2) receptor. Employing peptides to inhibit binding between SARS-CoV-2-RBD and ACE2-PD is a therapeutic solution for COVID-19. Previous experimental study found that 23-mer peptide (SBP1) bound to SARS-CoV-2-RBD with lower affinity than ACE2. To increase SBP1 affinity, our previous study used residues 21–45 of α1 helix of ACE2-PD (SPB25) to design peptides with predicted affinity better than SBP1 and SPB25 by increasing interactions of residues that do not form favorable interactions with SARS-CoV-2-RBD. To design SPB25 with better affinity than ACE2, we employed computational protein design to increase interactions of residues reported to form favorable interactions with SARS-CoV-2-RBD and combine newly designed mutations with the best single mutations from our previous study. Molecular dynamics show that predicted binding affinities of three peptides (SPB25 Q22R , SPB25 F8R/K11W/L25R and SPB25 F8R/K11F/Q22R/L25R ) are better than ACE2. Moreover, their predicted stabilities may be slightly higher than SBP1 as suggested by their helicities. This study developed an approach to design SARS-CoV-2 peptide binders with predicted binding affinities better than ACE2. These designed peptides are promising candidates as SARS-CoV-2 inhibitors.
【저자키워드】 Protein design, peptides, 【초록키워드】 COVID-19, SARS-CoV-2, ACE2, coronavirus, Mutation, COVID-19 pandemic, peptide, molecular dynamics, angiotensin-converting enzyme 2, inhibitors, binding affinity, Receptor binding domain, stability, therapeutic, receptor, binding, Interaction, S1 subunit, residue, domain, human cells, candidate, single mutation, SARS-CoV-2-RBD, approach, bind, predicted, reported, inhibit, suggested, α1 helix, 【제목키워드】 SARS-CoV-2, peptide, binding affinity, human ACE2 receptor, predicted,