Molecular Docking and Dynamics Studies to Explore Effective Inhibitory Peptides Against the Spike Receptor Binding Domain of SARS-CoV-2

Abstract

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic due to the high transmission and mortality rate of this virus. The world health and economic sectors have been severely affected by this deadly virus, exacerbated by the lack of sufficient efficient vaccines. The design of effective drug candidates and their rapid development is necessary to combat this virus. In this study, we selected 23 antimicrobial peptides from the literature and predicted their structure using PEP-FOLD 3.5. In addition, we docked them to the SARS-CoV-2 spike protein receptor-binding domain (RBD) to study their capability to inhibit the RBD, which plays a significant role in virus binding, fusion and entry into the host cell. We used several docking programs including HDOCK, HPEPDOCK, ClusPro, and HawkDock to calculate the binding energy of the protein-peptide complexes. We identified four peptides with high binding free energy and docking scores. The docking results were further verified by molecular dynamics (MD) simulations to characterize the protein-peptide complexes in terms of their root-mean-square fluctuation (RMSF), root-mean-square deviation (RMSD), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen bond formation. Allergenicity and toxicity predictions suggested that the peptides we identified were non-allergenic and non-toxic. This study suggests that these four antimicrobial peptides could inhibit the RBD of SARS-CoV-2. Future in vitro and in vivo studies are necessary to confirm this.

Evolutionary progression of collective mutations in Omicron sub-lineages towards efficient RBD-hACE2: Allosteric communications between and within viral and human proteins

“…Tyr508 is located just outside the RBM region at the N-terminus end of the β7. Tyr508 is involved in the RBD-hACE2 interaction [113] , [114] , binding and interaction with camel nanobodies for RBD neutralization [115] , standard drugs [116] , [117] , inhibitory peptides [118] , metal complexes [119] and natural inhibitory compounds [120] . Val510 binds a number of natural bioactive compounds with potential antiviral properties [116] , [121] , [122] .…”

The Inhibitory Potential of Ferulic Acid Derivatives against the SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics, and ADMET Evaluation

“…Analysis of the RMSF values allows the acquisition of an image of which residues are more flexible. As seen in Figure 12 c, the majority of residues have low RMSF values below 1 [ 120 , 122 ] while the terminal residues of the protease exhibit a much larger deviation and are the only ones to exceed 2.5 , with the exception of Arg222, Tyr154, Gln273, and Asp155 for compound e27. Therefore, the structure of the protein appears to be quite stable.…”

Evolutionary progression of collective mutations in Omicron sub-lineages towards efficient RBD-hACE2: allosteric communications between and within viral and human proteins

“…Tyr508 is located just outside the RBM region at the N-terminus end of the β7. Tyr508 is involved in the RBD-hACE2 interaction [113, 114], binding and interaction with camel nanobodies for RBD neutralization [115], standard drugs [116, 117], inhibitory peptides [118], metal complexes [119] and natural inhibitory compounds [120]. Val510 binds a number of natural bioactive compounds with potential antiviral properties [116, 121, 122].…”