Inhibitory Potential of Chromene Derivatives on Structural and Non-Structural Proteins of Dengue Virus
Abstract
:1. Introduction
2. Structure and Biology of Dengue Virus
3. Pathogenesis
4. Explorable Drug Targets
4.1. Viral Targets
4.1.1. Structural Proteins
Envelope Protein (E)
- Fusion inhibitors: Peptides and small molecules bound to the β-OG pocket. The peptidic inhibitors have poor absorption from the gastrointestinal tract; thus, intravenous administration is required.
- Glycosidase inhibitors: α-glycosidase inhibitors mainly target the glycosylation process. They are only employed in limited conditions due to their severe toxicity and lack of selectivity. Some examples are deoxynojirimycin (DNJ) and castanospermine (CSP).
- Carbohydrate-binding agents: These agents block the connection between the DENV envelope N-glycans and the host cell. Some examples include concanavalin A and wheat germ agglutinin.
PrM/Membrane Protein (M)
Capsid Protein (C)
Non-Structural Protein
4.2. Host Targets
5. Drugs under Clinical Trials
6. Vector Control
7. Treatment
8. Chromene Derivatives against Dengue Virus
8.1. Chromene Analogues Acting on NS-1
8.2. Chromene Analogues Acting on NS2B-NS3 Protease
8.3. Chromene Analogues Acting on NS5 Protein
8.4. Chromene Analogues Acting on Multiple Targets
8.4.1. Chromene Analogues Acting on DENV-2 My/DENV-E Protein
8.4.2. Chromene Analogues Acting on DENV Polymerase and DENV Protease
8.4.3. Chromene Analogues Acting on DENV E Protein and NS5
8.5. Chromene Analogues Acting on Furin Enzyme
8.6. Miscellaneous Reports
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Non-Structural Protein | Structural Features | Molecular Mass (KDa) | Functions |
---|---|---|---|
NS1 | Multifunctional protein with the exposed hydrophobic region. | 43–48 |
|
NS2A |
| 42 |
|
NS2B |
| 15 |
|
NS3 |
| 70 |
|
NS4A |
| 16 |
|
NS4B |
| 27 |
|
NS5 |
| 103 |
|
Drug | Sponsor | Trial Identifier | Phase | Location |
---|---|---|---|---|
AT-752 | Atea Pharmaceuticals, Inc. | NCT05366439 | I | New York, United States |
AT-752 in dengue infected patients | Atea Pharmaceuticals, Inc. | NCT05466240 | II | Brazil |
AT-752 in healthy subjects | Atea Pharmaceuticals, Inc. | NCT04722627 | I | Victoria, Australia |
JNJ-64281802 (For Dengue prevention) | Janssen Research & Development, LLC | NCT05201794 | II | Brazil |
JNJ-64281802 (With confirmed dengue fever patients) | Janssen Research & Development, LLC | NCT04906980 | II | Singapore |
JNJ-64281802 against DENV-3 | NIAID | NCT05048875 | II | Maryland and Vermont, United States |
Zanamivir–Prevent Vascular Permeability in Dengue (ZAP-DENGUE) | George Washington University | NCT04597437 | Early Phase I | - |
Ivermectin | Mahidol University | NCT02045069 | II/III | - |
Ivermectin in paediatric dengue patients | Mahidol University | NCT03432442 | II | Bangkok, Thailand |
Chloroquine | University of Sao Paulo | NCT00849602 | I/II | Ribeirão Preto, SP, Brazil |
Celgosivir | Singapore General Hospita | NCT01619969 | I/II | Singapore |
Melatonin | Ilocos Training and Regional Medical Centre | NCT05034809 | II | - |
Balapiravir | Hoffmann-La Roche | NCT01096576 | I | Ho Chi Minh City, Vietnam |
NT-proBNP and Troponin in Dengue children | Le PhoucTruyen | NCT04837430 | - | Ho Chi Minh City, Vietnam |
Montelukast | Phramongkutklao College of Medicine and Hospital | NCT04673422 | II/III | Bangkok and Songkhla, Thailand |
Ketotifen | National University Hospital, Singapore | NCT02673840 | IV | Singapore |
AV-1 | AbViro LLC | NCT04273217 | I | Texas, United States |
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Dharmapalan, B.T.; Biswas, R.; Sankaran, S.; Venkidasamy, B.; Thiruvengadam, M.; George, G.; Rebezov, M.; Zengin, G.; Gallo, M.; Montesano, D.; et al. Inhibitory Potential of Chromene Derivatives on Structural and Non-Structural Proteins of Dengue Virus. Viruses 2022, 14, 2656. https://doi.org/10.3390/v14122656
Dharmapalan BT, Biswas R, Sankaran S, Venkidasamy B, Thiruvengadam M, George G, Rebezov M, Zengin G, Gallo M, Montesano D, et al. Inhibitory Potential of Chromene Derivatives on Structural and Non-Structural Proteins of Dengue Virus. Viruses. 2022; 14(12):2656. https://doi.org/10.3390/v14122656
Chicago/Turabian StyleDharmapalan, Babitha Thekkiniyedath, Raja Biswas, Sathianarayanan Sankaran, Baskar Venkidasamy, Muthu Thiruvengadam, Ginson George, Maksim Rebezov, Gokhan Zengin, Monica Gallo, Domenico Montesano, and et al. 2022. "Inhibitory Potential of Chromene Derivatives on Structural and Non-Structural Proteins of Dengue Virus" Viruses 14, no. 12: 2656. https://doi.org/10.3390/v14122656
APA StyleDharmapalan, B. T., Biswas, R., Sankaran, S., Venkidasamy, B., Thiruvengadam, M., George, G., Rebezov, M., Zengin, G., Gallo, M., Montesano, D., Naviglio, D., & Shariati, M. A. (2022). Inhibitory Potential of Chromene Derivatives on Structural and Non-Structural Proteins of Dengue Virus. Viruses, 14(12), 2656. https://doi.org/10.3390/v14122656