Natural Flavonoid Derivatives Have Pan-Coronavirus Antiviral Activity
Abstract
:1. Introduction
2. Methods
2.1. Study Design
2.2. Chemistry
2.3. In Silico Screening of Natural Compounds
2.4. SARS-CoV-2 3CLpro Assay
2.5. Cell Viability Assay to Determine Compounds’ Toxicity
2.6. SARS-CoV-2 In Vitro Assay
2.7. SARS-CoV-2 Titration
2.8. Feline-CoV, Bovine-CoV, and HCoV-OC43 In Vitro Assays and Titration
2.9. Coronaviruses In Vitro Assays
2.10. Statistical Analysis
3. Results
3.1. Virtual Screening of the in-House Natural Products Library
3.2. SARS-CoV-2 3CLpro Assay
3.3. Effect of the 3CLpro Inhibitors on VERO E6 Viability
3.4. Antiviral Activity of 3CLpro Inhibitors against SARS-CoV-2
3.5. Effect of the 3CLpro Inhibitors on CRFK and HRT-18 Viability and Pan-Coronaviral Activity
3.6. Predicted Binding Mode of Most Effective SARS-CoV-2 3CLpro Inhibitors
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Basic Flavonoid Skeleton | ||||||
Mol. | Common Name | Chemical Structure | M.W. | Molecular Formula | Source | Reference |
Flavanones | ||||||
1 | Morin | 302.24 | C15H10O7 | Moriaceae family | [22] | |
2 | Quercetin | 302.24 | C15H10O7 | Ginkgo biloba (Ginkgoaceae family) Hypericum perforatum (Hypericaceae family) Sambucus canadensis (Adoxaceae family) | [23,24] | |
3 | Alnusin | 300.27 | C16H12O6 | Xerochrysum viscosum (Asteraceae family) Alnus sieboldiana (Betulaceae family) | [25] | |
4 | Isokaempferide | 300.27 | C16H12O6 | Amburana cearensis (Fabacee family) | [26] | |
5 | Galangin | 270.24 | C15H10O5 | Alpinia officinarum (Zingiberaceae family) Helichrysum aureonitens (Asteraceae family) Alpinia galanga (Zingiberaceae family) | [27,28,29] | |
Flavanones | ||||||
6 | Steppogenin | 288.26 | C15H12O6 | Euphorbia nicaeensis (Euforbiacee family) Maclura tricuspidata (Moraceae family) | [30] | |
7 | Sakuranetin | 286.28 | C16H14O5 | Polymnia fruticosa (Araliaceae family) | [31] | |
8 | Isosakuranetin | 286.28 | C16H14O5 | Monarda didyma (Lamiaceae family) | [32] | |
Flavones | ||||||
9 | Baicalein | 270.24 | C15H10O5 | Scutellaria baicalensis (Lamiaceae family) | [33] | |
10 | Hispidulin | 300.27 | C16H12O6 | Crossostephium chinense, Grindelia argentina and Saussurea involucrate (Asteraceae family) Arrabidaea chica (Bignoniaceae Family) | [34,35] | |
11 | Chrysin | 254.24 | C15H10O4 | Passiflora caerulea and Passiflora incarnata (Passifloraceae family) Oroxylum indicum (Bignoniaceae family) | [36] | |
Flavanonol | ||||||
12 | Taxifolin | 304.25 | C15H12O7 | Pinus roxburghii, Cedrus deodara (Pinaceae family) | [37] |
Compound | Molecular Model | Concentrations Tested (µg/mL) | Percentage of Inhibition of 3CLpro |
---|---|---|---|
Morin | Docking | 100.00 | 53.64 (33.85) |
50.00 | 18.64 (4.36) | ||
25.00 | <10 | ||
12.5 | <10 | ||
Baicalein | Docking | 100.00 | 94.72 (9.11) |
50.00 | 72.14 (7.75) | ||
25.00 | 25.57 (6.67) | ||
12.5 | 17.28 (1.11) | ||
Hispidulin | Docking | 100.00 | 55.62 (17.04) |
50.00 | 29.76 (12.56) | ||
25.00 | <10 | ||
12.5 | <10 | ||
Luteolin | Docking | 100.00 | 38.12 (2.32) |
50.00 | 30.88 (3.53) | ||
25.00 | <10 | ||
12.5 | <10 | ||
7,8-Dihydroxy-flavone | Docking | 100.00 | 39.8 (0.31) |
50.00 | 34.54 (0.13) | ||
25.00 | <10 | ||
12.5 | <10 | ||
Isokaempferide | Cluster | 100.00 | 49.98 (22.38) |
50.00 | 40.06 (27.12) | ||
25.00 | 19.69 (13.71) | ||
12.5 | <10 |
Compound | Concentrations Tested (µg/mL) | Antiviral Activity against F-CoV | Antiviral Activity against B-CoV | Antiviral Activity against OC43 |
---|---|---|---|---|
Baicalein | 100 | TX | TX | TX |
50 | 66.73 | 99.60 | 99.99 | |
25 | <50 | 89.85 | 99.99 | |
12.5 | <50 | <50 | 99.98 | |
6.25 | <50 | <50 | <50 | |
3.125 | <50 | <50 | <50 | |
1.56 | <50 | <50 | <50 | |
0.78 | <50 | <50 | <50 |
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Mori, M.; Quaglio, D.; Calcaterra, A.; Ghirga, F.; Sorrentino, L.; Cammarone, S.; Fracella, M.; D’Auria, A.; Frasca, F.; Criscuolo, E.; et al. Natural Flavonoid Derivatives Have Pan-Coronavirus Antiviral Activity. Microorganisms 2023, 11, 314. https://doi.org/10.3390/microorganisms11020314
Mori M, Quaglio D, Calcaterra A, Ghirga F, Sorrentino L, Cammarone S, Fracella M, D’Auria A, Frasca F, Criscuolo E, et al. Natural Flavonoid Derivatives Have Pan-Coronavirus Antiviral Activity. Microorganisms. 2023; 11(2):314. https://doi.org/10.3390/microorganisms11020314
Chicago/Turabian StyleMori, Mattia, Deborah Quaglio, Andrea Calcaterra, Francesca Ghirga, Leonardo Sorrentino, Silvia Cammarone, Matteo Fracella, Alessandra D’Auria, Federica Frasca, Elena Criscuolo, and et al. 2023. "Natural Flavonoid Derivatives Have Pan-Coronavirus Antiviral Activity" Microorganisms 11, no. 2: 314. https://doi.org/10.3390/microorganisms11020314