GC-MS, LC-MS/MS, Docking and Molecular Dynamics Approaches to Identify Potential SARS-CoV-2 3-Chymotrypsin-Like Protease Inhibitors from <i>Zingiber officinale</i> Roscoe
This study aims to identify and isolate the secondary metabolites of <i>Zingiber officinale</i> using GC-MS, preparative TLC, and LC-MS/MS methods, to evaluate the inhibitory potency on SARS-CoV-2 3 chymotrypsin-like protease enzyme, as well as to study the molecular interaction and stab...
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doaj-0420b32326a241cfb27aaa20adc879c42021-09-09T13:53:12ZengMDPI AGMolecules1420-30492021-08-01265230523010.3390/molecules26175230GC-MS, LC-MS/MS, Docking and Molecular Dynamics Approaches to Identify Potential SARS-CoV-2 3-Chymotrypsin-Like Protease Inhibitors from <i>Zingiber officinale</i> RoscoeMuhammad Sulaiman Zubair0Saipul Maulana1Agustinus Widodo2Ramadanil Pitopang3Muhammad Arba4Maywan Hariono5Department of Pharmacy, Faculty of Science, Tadulako University, Palu 94118, IndonesiaDepartment of Pharmacy, Faculty of Science, Tadulako University, Palu 94118, IndonesiaDepartment of Pharmacy, Faculty of Science, Tadulako University, Palu 94118, IndonesiaDepartment of Biology, Faculty of Science, Tadulako University, Palu 94118, IndonesiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Halu Oleo University, Kendari 93231, IndonesiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Sanata Darma University, Yogyakarta 55282, IndonesiaThis study aims to identify and isolate the secondary metabolites of <i>Zingiber officinale</i> using GC-MS, preparative TLC, and LC-MS/MS methods, to evaluate the inhibitory potency on SARS-CoV-2 3 chymotrypsin-like protease enzyme, as well as to study the molecular interaction and stability by using docking and molecular dynamics simulations. GC-MS analysis suggested for the isolation of terpenoids compounds as major compounds on methanol extract of pseudostems and rhizomes. Isolation and LC-MS/MS analysis identified 5-hydro-7, 8, 2′-trimethoxyflavanone (<b>9</b>), (<i>E</i>)-hexadecyl-ferulate (<b>1</b>), isocyperol (<b>2</b>), <i>N-</i>isobutyl-(2<i>E</i>,4<i>E</i>)-octadecadienamide (<b>3</b>), and nootkatone (<b>4</b>) from the rhizome extract, as well as from the leaves extract with the absence of <b>9</b>. Three known steroid compounds, i.e., spinasterone (<b>7</b>), spinasterol (<b>8</b>), and 24-methylcholesta-7-en-3<i>β</i>-on (<b>6</b>), were further identified from the pseudostem extract. Molecular docking showed that steroids compounds <b>7</b>, <b>8</b>, and <b>6</b> have lower predictive binding energies (MMGBSA) than other metabolites with binding energy of −87.91, −78.11, and −68.80 kcal/mole, respectively. Further characterization on the single isolated compound by NMR showed that <b>6</b> was identified and possessed 75% inhibitory activity on SARS-CoV-2 3CL protease enzyme that was slightly different with the positive control GC376 (77%). MD simulations showed the complex stability with compound <b>6</b> during 100 ns simulation time.https://www.mdpi.com/1420-3049/26/17/5230<i>Zingiber officinale</i>LC-MS/MSSteroids24-Methylcholesta-7-en-3β-on3CL ProteaseSARS-CoV-2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Muhammad Sulaiman Zubair Saipul Maulana Agustinus Widodo Ramadanil Pitopang Muhammad Arba Maywan Hariono |
spellingShingle |
Muhammad Sulaiman Zubair Saipul Maulana Agustinus Widodo Ramadanil Pitopang Muhammad Arba Maywan Hariono GC-MS, LC-MS/MS, Docking and Molecular Dynamics Approaches to Identify Potential SARS-CoV-2 3-Chymotrypsin-Like Protease Inhibitors from <i>Zingiber officinale</i> Roscoe Molecules <i>Zingiber officinale</i> LC-MS/MS Steroids 24-Methylcholesta-7-en-3β-on 3CL Protease SARS-CoV-2 |
author_facet |
Muhammad Sulaiman Zubair Saipul Maulana Agustinus Widodo Ramadanil Pitopang Muhammad Arba Maywan Hariono |
author_sort |
Muhammad Sulaiman Zubair |
title |
GC-MS, LC-MS/MS, Docking and Molecular Dynamics Approaches to Identify Potential SARS-CoV-2 3-Chymotrypsin-Like Protease Inhibitors from <i>Zingiber officinale</i> Roscoe |
title_short |
GC-MS, LC-MS/MS, Docking and Molecular Dynamics Approaches to Identify Potential SARS-CoV-2 3-Chymotrypsin-Like Protease Inhibitors from <i>Zingiber officinale</i> Roscoe |
title_full |
GC-MS, LC-MS/MS, Docking and Molecular Dynamics Approaches to Identify Potential SARS-CoV-2 3-Chymotrypsin-Like Protease Inhibitors from <i>Zingiber officinale</i> Roscoe |
title_fullStr |
GC-MS, LC-MS/MS, Docking and Molecular Dynamics Approaches to Identify Potential SARS-CoV-2 3-Chymotrypsin-Like Protease Inhibitors from <i>Zingiber officinale</i> Roscoe |
title_full_unstemmed |
GC-MS, LC-MS/MS, Docking and Molecular Dynamics Approaches to Identify Potential SARS-CoV-2 3-Chymotrypsin-Like Protease Inhibitors from <i>Zingiber officinale</i> Roscoe |
title_sort |
gc-ms, lc-ms/ms, docking and molecular dynamics approaches to identify potential sars-cov-2 3-chymotrypsin-like protease inhibitors from <i>zingiber officinale</i> roscoe |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2021-08-01 |
description |
This study aims to identify and isolate the secondary metabolites of <i>Zingiber officinale</i> using GC-MS, preparative TLC, and LC-MS/MS methods, to evaluate the inhibitory potency on SARS-CoV-2 3 chymotrypsin-like protease enzyme, as well as to study the molecular interaction and stability by using docking and molecular dynamics simulations. GC-MS analysis suggested for the isolation of terpenoids compounds as major compounds on methanol extract of pseudostems and rhizomes. Isolation and LC-MS/MS analysis identified 5-hydro-7, 8, 2′-trimethoxyflavanone (<b>9</b>), (<i>E</i>)-hexadecyl-ferulate (<b>1</b>), isocyperol (<b>2</b>), <i>N-</i>isobutyl-(2<i>E</i>,4<i>E</i>)-octadecadienamide (<b>3</b>), and nootkatone (<b>4</b>) from the rhizome extract, as well as from the leaves extract with the absence of <b>9</b>. Three known steroid compounds, i.e., spinasterone (<b>7</b>), spinasterol (<b>8</b>), and 24-methylcholesta-7-en-3<i>β</i>-on (<b>6</b>), were further identified from the pseudostem extract. Molecular docking showed that steroids compounds <b>7</b>, <b>8</b>, and <b>6</b> have lower predictive binding energies (MMGBSA) than other metabolites with binding energy of −87.91, −78.11, and −68.80 kcal/mole, respectively. Further characterization on the single isolated compound by NMR showed that <b>6</b> was identified and possessed 75% inhibitory activity on SARS-CoV-2 3CL protease enzyme that was slightly different with the positive control GC376 (77%). MD simulations showed the complex stability with compound <b>6</b> during 100 ns simulation time. |
topic |
<i>Zingiber officinale</i> LC-MS/MS Steroids 24-Methylcholesta-7-en-3β-on 3CL Protease SARS-CoV-2 |
url |
https://www.mdpi.com/1420-3049/26/17/5230 |
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