Antiviral Activity of Flavonoids from Geopropolis of the Brazilian Jandaira Bee against Zika and Dengue Viruses
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Geopropolis Sample and Flavonoid Isolation Process
2.3. Cells and Viruses
2.4. Cell Viability Assay
2.5. Antiviral Assay
2.6. Viral Titration
2.7. Statistical Analysis
3. Theoretical Methods
3.1. Molecular Docking
3.2. Enthalpy of Binding
3.3. Molecular Dynamics Simulation
3.4. Interaction Energy Analysis
4. Results
4.1. Identification of Flavonoids
4.2. Flavonoids’ Citotoxic Effects
4.3. Post-Treatment Antiviral Activity of Flavonoids
4.4. The Flavonoids Naringenin and 7-O-Methyl Naringenin Bind to the NS5-Methyltransferase of Both DENV and ZIKV
4.5. Molecular Dynamics Simulation Showed That Naringenin Forms a High Number of Non-Covalent Interactions at the Binding Site of NS5-Methyltransferase
5. Discussion
6. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Organism | PDB | Protein | Resolution (Å) | Reference |
---|---|---|---|---|
DENV-2 | 2BMF | NS3-helicase | 2.41 | [35] |
3U1I | NS3-protease | 2.30 | [36] | |
2P41 | NS5-methyltransferase | 1.80 | [37] | |
5K5M | NS5-RdRp | 2.00 | [38] | |
ZIKV | 5K8I | NS3-helicase | 1.69 | [39] |
5YOF | NS3-protease | 1.51 | [40] | |
5WZ2 | NS5-methyltransferase | 2.60 | [41] | |
6LD2 | NS5-RdRp | 1.40 | [42] |
Sample | Cytotoxicity a | |
---|---|---|
CC50 (µM/mL) | CC20 (µM/mL) | |
EtOH | 2.47 | 0.641 |
AcOEt | 2.29 | 0.293 |
Hexanic | 10.30 | 18.76 |
Naringenin | 241.6 | 86.43 |
7-O-methyl naringenin | 240.4 | 105.2 |
Positive control (6-MMPr) | 86.00 | 17.88 |
d# CC20 (μM/mL) | a# CC50 (μM/mL) | b# IC50 (μM/mL) | c# SI | |
---|---|---|---|---|
Naringenin | 86.43 | 241.6 | 58.89 | 4.1 |
7-O-methyl naringenin | 105.2 | 240.4 | 12.80 | 18.7 |
6-MMPr | 60.5 | 291 | 24.5 | 11.9 |
d# CC20 (μM/mL) | a# CC50 (μM/mL) | b# IC50 (μM/mL) | c# SI | |
---|---|---|---|---|
Naringenin | 86.43 | 241.6 | 42.91 | 5.6 |
7-O-methyl naringenin | 105.2 | 240.4 | 30.95 | 7.7 |
6-MMPr | 60.5 | 291 | 18.15 | 16.0 |
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Silva, P.G.d.; Chaves, E.J.F.; Silva, T.M.S.; Rocha, G.B.; Dantas, W.M.; Oliveira, R.N.d.; Pena, L.J. Antiviral Activity of Flavonoids from Geopropolis of the Brazilian Jandaira Bee against Zika and Dengue Viruses. Pharmaceutics 2023, 15, 2494. https://doi.org/10.3390/pharmaceutics15102494
Silva PGd, Chaves EJF, Silva TMS, Rocha GB, Dantas WM, Oliveira RNd, Pena LJ. Antiviral Activity of Flavonoids from Geopropolis of the Brazilian Jandaira Bee against Zika and Dengue Viruses. Pharmaceutics. 2023; 15(10):2494. https://doi.org/10.3390/pharmaceutics15102494
Chicago/Turabian StyleSilva, Poliana Gomes da, Elton José Ferreira Chaves, Tania Maria Sarmento Silva, Gerd Bruno Rocha, Willyenne Marília Dantas, Ronaldo Nascimento de Oliveira, and Lindomar José Pena. 2023. "Antiviral Activity of Flavonoids from Geopropolis of the Brazilian Jandaira Bee against Zika and Dengue Viruses" Pharmaceutics 15, no. 10: 2494. https://doi.org/10.3390/pharmaceutics15102494
APA StyleSilva, P. G. d., Chaves, E. J. F., Silva, T. M. S., Rocha, G. B., Dantas, W. M., Oliveira, R. N. d., & Pena, L. J. (2023). Antiviral Activity of Flavonoids from Geopropolis of the Brazilian Jandaira Bee against Zika and Dengue Viruses. Pharmaceutics, 15(10), 2494. https://doi.org/10.3390/pharmaceutics15102494