Table 1 Therapeutic interventions for DENV infection

Metabolic Pathway Inhibitors

Target glycolysis, lipid metabolism, amino acid metabolism and host glycoprotein processing to disrupt viral replication.

2-Deoxy-D-Glucose (2-DG), Metformin, 6-Amino-Nicotinamide (6-AN), FAS inhibitors, Celgosivir.

[48, 68, 127,128,129,130]

Drug Repurposing

Identify existing drugs that modulate immune-metabolic pathways.

Oxprenolol, Digoxin, Auranofin, Atorvastatin.

[131]

Natural Compounds

Use natural molecules with dual antiviral and anti-inflammatory effects.

Cordycepin (targets NS5 and NF-κB), Zileuton, Trimethadione, Linalool.

[132, 133]

RNA Replication Inhibitors

Target viral RNA replication mechanisms.

Sofosbuvir, JNJ-1802 (Mosnodenvir), EYU-688.

([134], NCT04906980, NCT06006559)

Host-Directed Therapies

Enhance host defenses and metabolic resilience against DENV.

Kinase inhibitors, Antioxidants, Niclosamide (nanoengineered for improved delivery).

[135, 136]

Immune Modulation

Fine-tune immune responses to reduce inflammation and enhance antiviral immunity.

Immune checkpoint inhibitors (PD-1, CTLA-4), IL-2 and IL-7 cytokines, Anti-inflammatory drugs (corticosteroids, IL-6 inhibitors).

[137,138,139,140,141]

Vaccination and Immune Priming

Develop vaccines and adjuvants targeting metabolic pathways to improve immune responses.

Next-generation vaccines (glycolysis/oxidative phosphorylation modulators), Metabolic adjuvants for DCs.

[148, 149, 157, 158]

Advanced Drug Delivery Systems

Improve delivery and bioavailability of therapeutic agents with poor solubility or stability.

Nanoengineered delivery of nucleic acid-based vaccines or repurposed drugs (e.g., Niclosamide).

[150,151,152,153,154]