Seleno-Functionalization of Quercetin Improves the Non-Covalent Inhibition of Mpro and Its Antiviral Activity in Cells against SARS-CoV-2
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis
2.2. Evaluation of Mpro Inhibition and Antiviral Assay
2.3. Molecular Docking of the Representative Compound 2d to SARS-CoV-2 Mpro
3. Materials and Methods
3.1. Synthesis: General Remarks
3.1.1. General Procedure for the In Situ Formation of RSeCl (5b–f)
3.1.2. General Procedure for the Seleno-Functionalization of 1
3.1.3. Physical Data
3.2. SARS-CoV-2 Mpro Expression and Purification
3.3. SARS-CoV-2 Mpro Proteolytic Activity Assay
3.4. SARS-CoV-2 Mpro Inhibition Assay
3.5. Molecular Simulations
3.6. Cells and Viruses
3.7. Evaluation of Viral Infection
3.8. Isolation of Nucleic Acids, Reverse Transcription, and Quantitative PCR
3.9. Cell Viability Assay
3.10. Statistical Analyses
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Entry | Electrophile (E) | Base (B) | 1:E:B | Time (h) | T (°C) | Yield % (2a:3) |
1 | PhSeCl | Tris | 1:2:5 | 72 | rt | 18 (18:traces) |
2 | PhSeOTf a | Tris | 1:2:5 | 24 | rt | 11 (8:3) |
3 | NPSeP | Tris | 1:2:5 | 4 | rt | 47 (22:25) |
4 | PhSeCl | Tris | 1:2:5 | 4 | 80 | 11 (11:trace) |
5 | NPSeP | Tris | 1:2:5 | 4 | 80 | 35 (10:25) |
6 b | PhSeCl | Tris | 1:2:5 | 2 | rt | 33 (33:trace) |
7 b | NPSeP | Tris | 1:2:5 | 1 | rt | 81 (30:51) |
8 b | PhSeCl | Tris | 1:2:10 | 2 | rt | 22 (22:trace) |
9 b | PhSeCl | Et3N | 1:2:5 | 2 | rt | 66 (55:11) |
10 b | PhSeCl | Arginine c | 1:2:5 | 2 | rt | 44 (44:trace) |
11 | PhSeCl | NaOH | 1:2:2 | 6 | rt | 9 (9:0) |
Entry | Product | Yield (%) |
---|---|---|
1 | 58 | |
2 | 48 | |
3 | 46 | |
4 | 32 | |
5 | 21 |
Ki (μM) | CI95,Ki | IC50 | CI95,IC50 | |
---|---|---|---|---|
Quercetin 1 | 7.4 | [5.8, 9.5] | 21 | [17, 28] |
2a | 1.8 | [1.4, 2.2] | 5.1 | [4.1, 6.3] |
2b | ND | ND | ||
2c | 8.6 | [6.9, 11] | 24 | [20, 31] |
2d | 3.8 | [3.0, 5.0] | 11 | [8.5, 14.2] |
2e | 1.1 | [0.85, 1,3] | 3.0 | [2.4, 3.9] |
3 | 4.6 | [3.7, 5.8] | 13 | [11, 16] |
6 | ND | ND | ||
7a | ND | ND | ||
8 | 1.1 | [0.80, 1.6] | 3.3 | [2.3, 4.8] |
9 | 0.77 | [0.57, 1.0] | 2.2 | [1.7, 3.2] |
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Mangiavacchi, F.; Botwina, P.; Menichetti, E.; Bagnoli, L.; Rosati, O.; Marini, F.; Fonseca, S.F.; Abenante, L.; Alves, D.; Dabrowska, A.; et al. Seleno-Functionalization of Quercetin Improves the Non-Covalent Inhibition of Mpro and Its Antiviral Activity in Cells against SARS-CoV-2. Int. J. Mol. Sci. 2021, 22, 7048. https://doi.org/10.3390/ijms22137048
Mangiavacchi F, Botwina P, Menichetti E, Bagnoli L, Rosati O, Marini F, Fonseca SF, Abenante L, Alves D, Dabrowska A, et al. Seleno-Functionalization of Quercetin Improves the Non-Covalent Inhibition of Mpro and Its Antiviral Activity in Cells against SARS-CoV-2. International Journal of Molecular Sciences. 2021; 22(13):7048. https://doi.org/10.3390/ijms22137048
Chicago/Turabian StyleMangiavacchi, Francesca, Pawel Botwina, Elena Menichetti, Luana Bagnoli, Ornelio Rosati, Francesca Marini, Sérgio F. Fonseca, Laura Abenante, Diego Alves, Agnieszka Dabrowska, and et al. 2021. "Seleno-Functionalization of Quercetin Improves the Non-Covalent Inhibition of Mpro and Its Antiviral Activity in Cells against SARS-CoV-2" International Journal of Molecular Sciences 22, no. 13: 7048. https://doi.org/10.3390/ijms22137048