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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.
- Source :
-
Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2024 Jul; Vol. 42 (11), pp. 5881-5894. Date of Electronic Publication: 2023 Jul 02. - Publication Year :
- 2024
-
Abstract
- This 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.Communicated by Ramaswamy H. Sarma.
- Subjects :
- Humans
Protein Binding
Binding Sites
Glucuronides chemistry
COVID-19 Drug Treatment
Hydrogen Bonding
Betacoronavirus drug effects
Coronavirus Infections drug therapy
Coronavirus Infections virology
Pandemics
Ligands
Molecular Dynamics Simulation
Molecular Docking Simulation
SARS-CoV-2 drug effects
Spike Glycoprotein, Coronavirus chemistry
Spike Glycoprotein, Coronavirus metabolism
Spike Glycoprotein, Coronavirus antagonists & inhibitors
Antiviral Agents chemistry
Antiviral Agents pharmacology
Flavanones chemistry
Flavanones pharmacology
COVID-19 virology
Subjects
Details
- Language :
- English
- ISSN :
- 1538-0254
- Volume :
- 42
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of biomolecular structure & dynamics
- Publication Type :
- Academic Journal
- Accession number :
- 37394802
- Full Text :
- https://doi.org/10.1080/07391102.2023.2229446