tetano
Editor, Senior Moderator
BMC Bioinformatics
. 2022 May 16;23(1):180.
doi: 10.1186/s12859-022-04724-9.
Molecular docking analysis reveals the functional inhibitory effect of Genistein and Quercetin on TMPRSS2: SARS-COV-2 cell entry facilitator spike protein
Reji Manjunathan[SUP] #[/SUP][SUP] 1 2 [/SUP], Vijayalakshmi Periyaswami[SUP] #[/SUP][SUP] 3 [/SUP], Kartik Mitra[SUP] 4 [/SUP], Arokiaraj Sherlin Rosita[SUP] 5 [/SUP], Medha Pandya[SUP] 6 [/SUP], Jayaraman Selvaraj[SUP] 7 [/SUP], Lokesh Ravi[SUP] 8 [/SUP], Nalini Devarajan[SUP] 9 [/SUP], Mukesh Doble[SUP] 10 11 [/SUP]
Affiliations
Abstract
Background: The Transmembrane Serine Protease 2 (TMPRSS2) of human cell plays a significant role in proteolytic cleavage of SARS-Cov-2 coronavirus spike protein and subsequent priming to the receptor ACE2. Approaching TMPRSS2 as a therapeutic target for the inhibition of SARS-Cov-2 infection is highly promising. Hence, in the present study, we docked the binding efficacy of ten naturally available phyto compounds with known anti-viral potential with TMPRSS2. The aim is to identify the best phyto compound with a high functional affinity towards the active site of the TMPRSS2 with the aid of two different docking software. Molecular Dynamic Simulations were performed to analyse the conformational space of the binding pocket of the target protein with selected molecules.
Results: Docking analysis using PyRx version 0.8 along with AutoDockVina reveals that among the screened phyto compounds, Genistein shows the maximum binding affinity towards the hydrophobic substrate-binding site of TMPRSS2 with three hydrogen bonds interaction ( - 7.5 kcal/mol). On the other hand, molecular docking analysis using Schrodinger identified Quercetin as the most potent phyto compound with a maximum binding affinity towards the hydrophilic catalytic site of TMPRSS2 ( - 7.847 kcal/mol) with three hydrogen bonds interaction. The molecular dynamics simulation reveals that the Quercetin-TMPRSS complex is stable until 50 ns and forms stable interaction with the protein ( - 22.37 kcal/mol of MM-PBSA binding free energy). Genistein creates a weak interaction with the loop residues and hence has an unstable binding and exits from the binding pocket.
Conclusion: The compounds, Quercetin and Genistein, can inhibit the TMPRSS2 guided priming of the spike protein. The compounds could reduce the interaction of the host cell with the type I transmembrane glycoprotein to prevent the entry of the virus. The critical finding is that compared to Genistein, Quercetin exhibits higher binding affinity with the catalytic unit of TMPRSS2 and forms a stable complex with the target. Thus, enhancing our innate immunity by consuming foods rich in Quercetin and Genistein or developing a novel drug in the combination of Quercetin and Genistein could be the brilliant choices to prevent SARS-Cov-2 infection when we consider the present chaos associated with vaccines and anti-viral medicines.
Keywords: Bioinformatics tools; Molecular docking; Molecular dynamics; Phyto compounds; SARS-Cov-2 coronavirus; Transmembrane serine protease 2.
. 2022 May 16;23(1):180.
doi: 10.1186/s12859-022-04724-9.
Molecular docking analysis reveals the functional inhibitory effect of Genistein and Quercetin on TMPRSS2: SARS-COV-2 cell entry facilitator spike protein
Reji Manjunathan[SUP] #[/SUP][SUP] 1 2 [/SUP], Vijayalakshmi Periyaswami[SUP] #[/SUP][SUP] 3 [/SUP], Kartik Mitra[SUP] 4 [/SUP], Arokiaraj Sherlin Rosita[SUP] 5 [/SUP], Medha Pandya[SUP] 6 [/SUP], Jayaraman Selvaraj[SUP] 7 [/SUP], Lokesh Ravi[SUP] 8 [/SUP], Nalini Devarajan[SUP] 9 [/SUP], Mukesh Doble[SUP] 10 11 [/SUP]
Affiliations
- PMID: 35578172
- DOI: 10.1186/s12859-022-04724-9
Abstract
Background: The Transmembrane Serine Protease 2 (TMPRSS2) of human cell plays a significant role in proteolytic cleavage of SARS-Cov-2 coronavirus spike protein and subsequent priming to the receptor ACE2. Approaching TMPRSS2 as a therapeutic target for the inhibition of SARS-Cov-2 infection is highly promising. Hence, in the present study, we docked the binding efficacy of ten naturally available phyto compounds with known anti-viral potential with TMPRSS2. The aim is to identify the best phyto compound with a high functional affinity towards the active site of the TMPRSS2 with the aid of two different docking software. Molecular Dynamic Simulations were performed to analyse the conformational space of the binding pocket of the target protein with selected molecules.
Results: Docking analysis using PyRx version 0.8 along with AutoDockVina reveals that among the screened phyto compounds, Genistein shows the maximum binding affinity towards the hydrophobic substrate-binding site of TMPRSS2 with three hydrogen bonds interaction ( - 7.5 kcal/mol). On the other hand, molecular docking analysis using Schrodinger identified Quercetin as the most potent phyto compound with a maximum binding affinity towards the hydrophilic catalytic site of TMPRSS2 ( - 7.847 kcal/mol) with three hydrogen bonds interaction. The molecular dynamics simulation reveals that the Quercetin-TMPRSS complex is stable until 50 ns and forms stable interaction with the protein ( - 22.37 kcal/mol of MM-PBSA binding free energy). Genistein creates a weak interaction with the loop residues and hence has an unstable binding and exits from the binding pocket.
Conclusion: The compounds, Quercetin and Genistein, can inhibit the TMPRSS2 guided priming of the spike protein. The compounds could reduce the interaction of the host cell with the type I transmembrane glycoprotein to prevent the entry of the virus. The critical finding is that compared to Genistein, Quercetin exhibits higher binding affinity with the catalytic unit of TMPRSS2 and forms a stable complex with the target. Thus, enhancing our innate immunity by consuming foods rich in Quercetin and Genistein or developing a novel drug in the combination of Quercetin and Genistein could be the brilliant choices to prevent SARS-Cov-2 infection when we consider the present chaos associated with vaccines and anti-viral medicines.
Keywords: Bioinformatics tools; Molecular docking; Molecular dynamics; Phyto compounds; SARS-Cov-2 coronavirus; Transmembrane serine protease 2.