Repository logo
 
Publication

Naringenin-4'-glucuronide as a new drug candidate against the COVID-19 Omicron variant: a study based on molecular docking, molecular dynamics, MM/PBSA and MM/GBSA

2024-07Journal article Embargoed access
Simple item page
dc.contributor.authorCobre, Alexandre de Fátima
dc.contributor.authorNeto, Moisés Maia
dc.contributor.authorMelo, Eduardo Borges de
dc.contributor.authorFachi, Mariana Millan
dc.contributor.authorFerreira, Luana Mota
dc.contributor.authorTonin, Fernanda
dc.contributor.authorPontarolo, Roberto
dc.date.accessioned2023-08-01T15:53:09Z
dc.date.embargo2025-08-01
dc.date.issued2024-07
dc.description.abstractThis study aimed to identify natural bioactive compounds (NBCs) as potential inhibitors of the spike (S1) receptor binding domain (RBD) of the COVID-19 Omicron variant using computer simulations (in silico). NBCs with previously proven biological in vitro activity were obtained from the ZINC database and analyzed through virtual screening, molecular docking, molecular dynamics (MD), molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA), and molecular mechanics/generalized Born surface area (MM/GBSA). Remdesivir was used as a reference drug in docking and MD calculations. A total of 170,906 compounds were analyzed. Molecular docking screening revealed the top four NBCs with a high affinity with the spike (affinity energy <-7 kcal/mol) to be ZINC000045789238, ZINC000004098448, ZINC000008662732, and ZINC000003995616. In the MD analysis, the four ligands formed a complex with the highest dynamic equilibrium S1 (mean RMSD <0.3 nm), lowest fluctuation of the complex amino acid residues (RMSF <1.3), and solvent accessibility stability. However, the ZINC000045789238-spike complex (naringenin-4'-O glucuronide) was the only one that simultaneously had minus signal (-) MM/PBSA and MM/GBSA binding free energy values (-3.74 kcal/mol and -15.65 kcal/mol, respectively), indicating favorable binding. This ligand (naringenin-4'-O glucuronide) was also the one that produced the highest number of hydrogen bonds in the entire dynamic period (average = 4601 bonds per nanosecond). Six mutant amino acid residues formed these hydrogen bonds from the RBD region of S1 in the Omicron variant: Asn417, Ser494, Ser496, Arg403, Arg408, and His505. Naringenin-4'-O-glucuronide showed promising results as a potential drug candidate against COVID-19. In vitro, and preclinical studies are needed to confirm these findings.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCobre AF, Neto MM, Melo EB, Fachi MM, Ferreira LM, Tonin FS, et al. Naringenin-4'-glucuronide as a new drug candidate against the COVID-19 Omicron variant: a study based on molecular docking, molecular dynamics, MM/PBSA and MM/GBSA. J Biomol Struct Dyn. 2024;42(11):5881-94.pt_PT
dc.identifier.doi10.1080/07391102.2023.2229446pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/16357
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherTaylor & Francispt_PT
dc.relation.publisherversionhttps://www.tandfonline.com/doi/full/10.1080/07391102.2023.2229446pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectNaringenin-4'-glucuronidept_PT
dc.subjectSARS-CoV-2pt_PT
dc.subjectIn silicopt_PT
dc.subjectSpike proteinpt_PT
dc.subjectTreatmentpt_PT
dc.titleNaringenin-4'-glucuronide as a new drug candidate against the COVID-19 Omicron variant: a study based on molecular docking, molecular dynamics, MM/PBSA and MM/GBSApt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage14pt_PT
oaire.citation.endPage5894pt_PT
oaire.citation.issue11pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.startPage5881pt_PT
oaire.citation.titleJournal of Biomolecular Structure and Dynamicspt_PT
oaire.citation.volume42pt_PT
person.familyNameTonin
person.givenNameFernanda
person.identifier.ciencia-idD01C-C700-9411
person.identifier.orcid0000-0003-4262-8608
person.identifier.ridO-2050-2017
person.identifier.scopus-author-id56085115800
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication61ded30e-ecec-4b3e-b953-2293e080ebdd
relation.isAuthorOfPublication.latestForDiscovery61ded30e-ecec-4b3e-b953-2293e080ebdd

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Naringenin-4'-glucuronide as a new drug candidate against the COVID-19 Omicron variant_a study based on molecular docking, molecular dynamics.pdf
Size:
3.02 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

ESTeSL - Artigos