Abstract
The Spike receptor binding domain (S-RBD) from SARS-CoV-2, a crucial protein for the entrance of the virus into target cells is known to cause infection by binding to a cell surface protein. Hence, reckoning therapeutics for the S-RBD of SARS-CoV-2 may address a significant way to target viral entry into the host cells. Herein, through in-silico approaches (Molecular docking, molecular dynamics (MD) simulations, and end-state thermodynamics), we aimed to screen natural molecules from different plants for their ability to inhibit S-RBD of SARS-CoV-2. We prioritized the best interacting molecules (Diacetylcurcumin and Dicaffeoylquinic acid) by analysis of protein-ligand interactions and subjected them for long-term MD simulations. We found that Dicaffeoylquinic acid interacted prominently with essential residues (Lys417, Gln493, Tyr489, Phe456, Tyr473, and Glu484) of S-RBD. These residues are involved in interactions between S-RBD and ACE2 and could inhibit the viral entry into the host cells. The in-silico analyses indicated that Dicaffeoylquinic acid and Diacetylcurcumin might have the potential to act as inhibitors of SARS-CoV-2 S-RBD. The present study warrants further in-vitro and in-vivo studies of Dicaffeoylquinic acid and Diacetylcurcumin for validation and acceptance of their inhibitory potential against S-RBD of SARS-CoV-2.
Keywords: ACE2; Dicaffeoylquinic acid; Ensemble clustering; MM-PBSA; S-RBD.
【저자키워드】 ACE2, MM-PBSA, Dicaffeoylquinic acid, Ensemble clustering, S-RBD., 【초록키워드】 SARS-CoV-2, spike, Therapeutics, Infection, molecular docking, docking, molecular dynamics, virus, inhibitors, viral entry, MD simulations, Receptor binding domain, Protein, S-RBD, molecular, plant, in-silico, binding, Interaction, Analysis, acceptance, In-vitro, host cells, target cells, target cell, Spike receptor binding domain, inhibitors of SARS-CoV-2, residue, protein-ligand interactions, inhibitory, surface protein, approach, protein-ligand interaction, Cell, involved, indicated, inhibit, 【제목키워드】 SARS-CoV-2, spike, human ACE2, Protein, inhibitor, identification,