Computational Design of a Potential Therapeutic Peptide Against Spike Protein of SARS-CoV-2

Abstract

SARS-CoV-2 entrance to the host cells is started by the interaction between receptor binding domain (RBD) of the spike (S) protein on the virus with the angiotensin-converting enzyme 2 (ACE2) receptor which is very important in the onset of viral infection. Interference with this interaction can be a promising way to prevent Covid-19 infection. In this study, a novel potential therapeutic peptide was designed in silico based on the key interacting amino acids of ACE2 against SARS-CoV-2 S protein. In our computational analysis, a peptide consisting of residues 19-48 of ACE2 was chosen as the wild-type peptide. Based on this peptide, six mutant peptides (MuP1-6) were designed and then assessed in term of interaction with S protein. The result of protein-peptide docking by HADDOCK web server and then immunological analysis by SVMTriP epitope prediction tool leads to choose MuP3 as the best mutant. Molecular dynamics simulations of wild-type peptide-S protein complex and MuP3-S protein complex, showed MuP3 has better interaction with S protein than wild type peptide (interaction energies -897.14 vs. -784.13 (kJ/mol)) which can be a potential therapeutic peptide for Covid-19 pandemic. The aim of this study was design of a therapeutic peptide against SARS-CoV-2 S protein. Six mutant peptides (MuP1-6) were designed and then their interaction potential with S protein was assessed by molecular docking and molecular dynamics which MuP3 showed the properties of a potential therapeutic peptide.