A phytochemical-based medication search for the SARS-CoV-2 infection by molecular docking models towards spike glycoproteins and main proteases
This journal is © The Royal Society of Chemistry..
Identifying best bioactive phytochemicals from different medicinal plants using molecular docking techniques demonstrates a potential pre-clinical compound discovery against SARS-CoV-2 viral infection. The in silico screening of bioactive phytochemicals with the two druggable targets of SARS-CoV-2 by simple precision/extra precision molecular docking methods was used to compute binding affinity at its active sites. phyllaemblicin and cinnamtannin class of phytocompounds showed a better binding affinity range (-9.0 to -8.0 kcal mol-1) towards both these SARS-CoV-2 targets; the corresponding active site residues in the spike protein were predicted as: Y453, Q496, Q498, N501, Y449, Q493, G496, T500, Y505, L455, Q493, and K417; and Mpro: Q189, H164, H163, P168, H41, L167, Q192, M165, C145, Y54, M49, and Q189. Molecular dynamics simulation further established the structural and energetic stability of protein-phytocompound complexes and their interactions with their key residues supporting the molecular docking analysis. Protein-protein docking using ZDOCK and Prodigy server predicted the binding pose and affinity (-13.8 kcal mol-1) of the spike glycoprotein towards the human ACE2 enzyme and also showed significant structural variations in the ACE2 recognition site upon the binding of phyllaemblicin C compound at their binding interface. The phyllaemblicin and cinnamtannin class of phytochemicals can be potential inhibitors of both the spike and Mpro proteins of SARS-CoV-2; furthermore, its pharmacology and clinical optimization would lead towards novel COVID-19 small-molecule therapy.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
|---|---|
| Enthalten in: |
RSC advances - 11(2021), 20 vom: 23. März, Seite 12003-12014 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Pushkaran, Anju Choorakottayil [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 08.11.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1039/d0ra10458b |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM339532432 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM339532432 | ||
| 003 | DE-627 | ||
| 005 | 20231226003116.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1039/d0ra10458b |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1131.xml |
| 035 | |a (DE-627)NLM339532432 | ||
| 035 | |a (NLM)35423778 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Pushkaran, Anju Choorakottayil |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A phytochemical-based medication search for the SARS-CoV-2 infection by molecular docking models towards spike glycoproteins and main proteases |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 08.11.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a This journal is © The Royal Society of Chemistry. | ||
| 520 | |a Identifying best bioactive phytochemicals from different medicinal plants using molecular docking techniques demonstrates a potential pre-clinical compound discovery against SARS-CoV-2 viral infection. The in silico screening of bioactive phytochemicals with the two druggable targets of SARS-CoV-2 by simple precision/extra precision molecular docking methods was used to compute binding affinity at its active sites. phyllaemblicin and cinnamtannin class of phytocompounds showed a better binding affinity range (-9.0 to -8.0 kcal mol-1) towards both these SARS-CoV-2 targets; the corresponding active site residues in the spike protein were predicted as: Y453, Q496, Q498, N501, Y449, Q493, G496, T500, Y505, L455, Q493, and K417; and Mpro: Q189, H164, H163, P168, H41, L167, Q192, M165, C145, Y54, M49, and Q189. Molecular dynamics simulation further established the structural and energetic stability of protein-phytocompound complexes and their interactions with their key residues supporting the molecular docking analysis. Protein-protein docking using ZDOCK and Prodigy server predicted the binding pose and affinity (-13.8 kcal mol-1) of the spike glycoprotein towards the human ACE2 enzyme and also showed significant structural variations in the ACE2 recognition site upon the binding of phyllaemblicin C compound at their binding interface. The phyllaemblicin and cinnamtannin class of phytochemicals can be potential inhibitors of both the spike and Mpro proteins of SARS-CoV-2; furthermore, its pharmacology and clinical optimization would lead towards novel COVID-19 small-molecule therapy | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Nath En, Prajeesh |e verfasserin |4 aut | |
| 700 | 1 | |a Melge, Anu R |e verfasserin |4 aut | |
| 700 | 1 | |a Puthiyedath, Rammanohar |e verfasserin |4 aut | |
| 700 | 1 | |a Mohan, C Gopi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t RSC advances |d 2011 |g 11(2021), 20 vom: 23. März, Seite 12003-12014 |w (DE-627)NLM218315961 |x 2046-2069 |7 nnns |
| 773 | 1 | 8 | |g volume:11 |g year:2021 |g number:20 |g day:23 |g month:03 |g pages:12003-12014 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1039/d0ra10458b |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 11 |j 2021 |e 20 |b 23 |c 03 |h 12003-12014 | ||