A multi-targeted approach to identify potential flavonoids against three targets in the SARS-CoV-2 life cycle.
3CLpro
COVID-19
COVID-19 drug discovery
Computational studies
Glycosylated flavonoids
Hesperidin
In silico
Naringin
Natural products
PLpro
SARS-CoV-2
TMPRSS2
Journal
Computers in biology and medicine
ISSN: 1879-0534
Titre abrégé: Comput Biol Med
Pays: United States
ID NLM: 1250250
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
12
11
2021
revised:
08
01
2022
accepted:
08
01
2022
pubmed:
16
1
2022
medline:
17
2
2022
entrez:
15
1
2022
Statut:
ppublish
Résumé
The advent and persistence of the Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2)-induced Coronavirus Disease (COVID-19) pandemic since December 2019 has created the largest public health emergency in over a century. Despite the administration of multiple vaccines across the globe, there continues to be a lack of approved efficacious non-prophylactic interventions for the disease. Flavonoids are a class of phytochemicals with historically established antiviral, anti-inflammatory and antioxidative properties that are effective against cancers, type 2 diabetes mellitus, and even other human coronaviruses. To identify the most promising bioactive flavonoids against the SARS-CoV-2, this article screened a virtual library of 46 bioactive flavonoids against three promising targets in the SARS-CoV-2 life cycle: human TMPRSS2 protein, 3CLpro, and PLpro. By examining the effects of glycosylation and other structural-activity relationships, the presence of sugar moiety in flavonoids significantly reduces its binding energy. It increases the solubility of flavonoids leading to reduced toxicity and higher bioavailability. Through protein-ligand contact profiling, it was concluded that naringin formed more hydrogen bonds with TMPRSS2 and 3CLpro. In contrast, hesperidin formed a more significant number of hydrogen bonds with PLpro. These observations were complimented by the 100 ns molecular dynamics simulation and binding free energy analysis, which showed a considerable stability of docked bioflavonoids in the active site of SARS-CoV-2 target proteins. Finally, the binding affinity and stability of the selected docked complexes were compared with the reference ligands (camostat for TMPRSS2, GC376 for 3CLpro, and GRL0617 for PLpro) that strongly inhibit their respective SARS-COV-2 targets. Overall analysis revealed that the selected flavonoids could be potential therapeutic agents against SARS-CoV-2. Naringin showed better affinity and stability for TMPRSS2 and 3CLpro, whereas hesperidin showed a better binding relationship and stability for PLpro.
Identifiants
pubmed: 35032740
pii: S0010-4825(22)00023-3
doi: 10.1016/j.compbiomed.2022.105231
pmc: PMC8750703
pii:
doi:
Substances chimiques
5-amino-2-methyl-N-((R)-1-(1-naphthyl)ethyl)benzamide
0
Aniline Compounds
0
Benzamides
0
Flavonoids
0
Naphthalenes
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105231Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Références
Mil Med Res. 2020 Mar 13;7(1):11
pubmed: 32169119
Nat Rev Microbiol. 2021 Mar;19(3):155-170
pubmed: 33116300
Nutrients. 2021 Aug 16;13(8):
pubmed: 34444960
J Prev Med Hyg. 2020 Oct 06;61(3):E304-E312
pubmed: 33150219
Phytochem Rev. 2021 May 22;:1-22
pubmed: 34054380
Drug Des Devel Ther. 2015 Aug 19;9:4761-78
pubmed: 26316713
Nature. 2020 Jun;582(7811):289-293
pubmed: 32272481
Commun Biol. 2021 Jan 20;4(1):93
pubmed: 33473151
Exp Mol Med. 2021 May;53(5):956-972
pubmed: 34035463
Pharmaceuticals (Basel). 2019 Jan 10;12(1):
pubmed: 30634637
Pharmaceuticals (Basel). 2021 Jun 07;14(6):
pubmed: 34200456
Nat Commun. 2020 Sep 4;11(1):4417
pubmed: 32887884
Chem Biol Interact. 2020 Sep 1;328:109211
pubmed: 32735799
J Biomol Struct Dyn. 2021 Apr;39(7):2338-2351
pubmed: 32216596
Nat Commun. 2021 Feb 2;12(1):743
pubmed: 33531496
Nucleic Acids Res. 2021 Jan 8;49(D1):D1388-D1395
pubmed: 33151290
J Clin Pharmacol. 2022 Mar;62(3):291-303
pubmed: 34921562
Int J Mol Sci. 2021 Apr 12;22(8):
pubmed: 33921228
Virus Res. 2020 Nov;289:198146
pubmed: 32866534
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
AIMS Public Health. 2021 Feb 1;8(1):137-153
pubmed: 33575413
J Adv Res. 2020 Mar 16;24:91-98
pubmed: 32257431
J Biomol Struct Dyn. 2021 Jun 28;:1-17
pubmed: 34182889
New Microbes New Infect. 2020 Apr 14;35:100679
pubmed: 32322401
J Cell Mol Med. 2022 Feb;26(3):636-653
pubmed: 34967105
Sci Rep. 2017 Mar 03;7:42717
pubmed: 28256516
Sci Rep. 2019 Dec 13;9(1):19059
pubmed: 31836806
Genes (Basel). 2021 Apr 19;12(4):
pubmed: 33921689
Nucleic Acids Res. 2015 Jul 1;43(W1):W448-54
pubmed: 25855812
J Pharm Anal. 2020 Aug;10(4):313-319
pubmed: 32296570
Lancet Infect Dis. 2020 May;20(5):533-534
pubmed: 32087114
J Virol. 2013 Jun;87(12):7039-45
pubmed: 23596293
Viruses. 2019 Mar 02;11(3):
pubmed: 30832341
Methods Mol Biol. 2020;2203:1-29
pubmed: 32833200
Biomed Pharmacother. 2018 Nov;107:1128-1134
pubmed: 30257325
Front Pharmacol. 2021 Jan 20;11:621099
pubmed: 33708124
Crit Rev Food Sci Nutr. 2017 Jun 13;57(9):1874-1905
pubmed: 26176651
Cardiovasc Revasc Med. 2021 Apr 15;:
pubmed: 33952432
EBioMedicine. 2021 Mar;65:103255
pubmed: 33676899
Virol J. 2011 Dec 28;8:560
pubmed: 22201648
FEBS J. 2007 Apr;274(8):2148-60
pubmed: 17388811
Front Microbiol. 2020 Jul 14;11:1723
pubmed: 32765482
Nat Commun. 2021 Jan 20;12(1):488
pubmed: 33473130
Nucleic Acids Res. 2018 Jul 2;46(W1):W257-W263
pubmed: 29718510
Med Hypotheses. 2020 Nov;144:109957
pubmed: 32531538
Int J Mol Sci. 2021 Oct 14;22(20):
pubmed: 34681727
Am J Pathol. 2010 Jun;176(6):2986-96
pubmed: 20382709