Identification of potential plant bioactive as SARS-CoV-2 Spike protein and human ACE2 fusion inhibitors. (September 2021)

• Record Type: Journal Article
• Authors: Singh, Rahul; Bhardwaj, Vijay Kumar; Sharma, Jatin; Kumar, Dinesh; Purohit, Rituraj
• Is Part Of: Computers in biology and medicine. Volume 136(2021)
• Publication Date: 2021-09
• Subjects: S-RBD -- ACE2 -- Ensemble clustering -- MM-PBSA -- Dicaffeoylquinic acid; Medicine -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; 610.285
• DOI: 10.1016/j.compbiomed.2021.104631
• Languages: English
• ISSNs: 0010-4825

Abstract

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. Graphical abstract: Image 1 Highlights: Spike receptor protein assists entry of SARS-CoV-2 into the host cell (ACE2). 33 bioactive molecules were screened for their interaction with SARS-CoV-2 S-RBD. Molecular docking filtered out two molecules that strongly bind to S-RBD. End state thermodynamics identified Dicaffeoylquinic acid as hit molecule.