Mapping of ACE2 binding site on SARS-CoV-2 spike protein S1: docking study with peptides

Abstract

Among different approaches to control the COVID19 disease, there is clear interest to develop inhibitors which block the virus interaction with the host cells and through this simple mechanism could facilitate developing medication. In this report, interaction of the virus SARS CoV2 spike protein S1 binding site with potential antiviral peptide ligands is analysed computationally. The peptides are derived from the binding domain of the angiotensinconverting enzyme 2, which is the receptor site for this virus. These calculations reveal that although shortening of these peptides from the N terminus and C terminus reduces their docking energy on the S1 binding site, there is still a number of peptides which effectively bind to the binding site on the SARS CoV2 spike protein S1, and thus can be used as leads for further optimization of the inhibitory effect. Finally, this may open new perspectives for working out treatments against the virus infection.

Mapping the ACE2 binding site on the SARS-CoV-2 spike protein S1: molecular recognition pattern

“…The docking energy values were calculated and further processed by using con ventional quantitative structure-activity analysis methods. The para meters and the procedure of the MD simulations were described in detail in our previous work [7].…”

“…As ACE2 is physiologically im portant for the functioning of the host cell, inhibition of the virus binding site on this enzyme by using peptides derived from the Sprotein structure, as proposed in [5], has understandable shortcomings. However, these do not apply in the case of peptides that mimic the ACE2 struc ture and inhibit the virus-receptor interaction by binding with the receptorbinding domain (RBD) on the S1 protein [6,7]. Therefore, this study, as well as our previous work [7], was focused on the design of such inhibitory peptides by using computational methods.…”

“…However, these do not apply in the case of peptides that mimic the ACE2 struc ture and inhibit the virus-receptor interaction by binding with the receptorbinding domain (RBD) on the S1 protein [6,7]. Therefore, this study, as well as our previous work [7], was focused on the design of such inhibitory peptides by using computational methods.…”

“…It can be suggested that the most straightforward de sign of effective peptide inhibitors that target the binding site on the S1 protein can be made proceeding from the peptide sequence of the virus binding domain of the ACE2 molecule [7]. The viability of this approach is based on the availability of structural data for proteins S1 and ACE2 and their complex [3,5], published as '6LZG' in the Worldwide Protein Data Bank (PDB) database (www.pdb.org).…”

“…Following [6], in our earlier study [7] we mapped the α1 domain binding site on the S1 protein using com putational docking analysis; in that study the peptide sequence 19-45 of the Nterminal part of ACE2 (STIEEQ AKTFLDKFNHEAEDLFYQSS) was truncated from both ends, and the docking of 200 peptide fragments at the binding site on the S1 protein was analysed. We found that the α1 domain sequence can be shortened to a certain extent without significant reduction of the docking energy, which is 'good news' for therapeutic peptide development [8].…”