5-Aminolevulinic acid (5-ALA) is a non-protein amino acid and a key precursor in chlorophyll and heme biosynthesis. It functions as a plant growth regulator and metabolic modulator. Recent studies have shown that it also acts as a plant immune inducer with antiviral properties. When used in combination with antiviral agents, 5-ALA enhances virus resistance through multi-target, multi-pathway actions, reducing chemical usage and minimizing the risk of resistance development.
What is 5-ALA?
5-ALA plays a regulatory role in plant metabolism, improving growth, stress tolerance, and quality. In plants, it converts into protoporphyrin IX (PPIX), which has shown antiviral activity against various viruses such as Zika virus, Dengue virus, and Influenza A. It is also a precursor to heme, which induces heme oxygenase-1 (HO-1) and has therapeutic value in viral infections like COVID-19.
Synergistic Mechanisms with Antiviral Agents
1. Immune Signaling Activation
5-ALA activates salicylic acid (SA) and jasmonic acid (JA) pathways, enhancing systemic acquired resistance (SAR). Antiviral agents suppress virus replication. Together, they form a dual “immune + direct” defense mechanism.
2. Antioxidant System Enhancement
5-ALA boosts antioxidant enzyme activities such as SOD and POD, mitigating oxidative stress caused by viral infection. This creates a favorable internal environment for antiviral agents.
3. Direct Viral Inhibition
- Interferes with viral RNA/DNA replication and capsid protein assembly.
- Reduces virus movement between cells by affecting plasmodesmata function.
4. Enhanced Absorption and Utilization of Antivirals
- Regulates stomatal behavior and cuticle structure, improving foliar permeability.
- Prolongs efficacy by enhancing photosynthesis and metabolic activity, slowing degradation of chemical agents.
5. Multi-Target Virus Suppression
- Antiviral drugs inhibit viral polymerase or coat proteins, while 5-ALA suppresses virus movement proteins (MP).
- Reduced reliance on single agents lowers mutation-driven resistance.
6. Promotes Plant Growth and Recovery
5-ALA increases chlorophyll content and photosynthesis efficiency, improving overall plant vigor and resistance to virus-related damage.
Application Studies and Case Reports
1. Combined Use with Chemical Antivirals
- Ribavirin + 5-ALA: In TMV-infected tobacco, 50 mg/L 5-ALA with low-dose ribavirin increased suppression rate by over 30% while reducing phytotoxicity.
- Ningnanmycin + 5-ALA: In TYLCV-infected tomato, co-application reduced viral load and boosted yield by 15–20%.
2. Combined Use with Biopesticides
- Chitosan + 5-ALA: Induces expression of antiviral genes (e.g., NPR1, PR1), enhancing control of CMV.
- Plant Extracts + 5-ALA: Improves suppression of PVY and reduces virus accumulation in phloem.
5-ALA Against SARS-CoV-2: Laboratory Research
Research by Nagasaki University demonstrated that 5-ALA effectively inhibited SARS-CoV-2 in vitro.
- VeroE6 and Caco-2 cells: Virus load dropped significantly after 72h treatment with 1000–2000μM 5-ALA.
- Effect was dose-dependent and confirmed by fluorescence imaging.
- Combined use with sodium ferrous citrate (SFC) enhanced antiviral action.
Advantages of 5-ALA in Antiviral Programs
- Reduced Chemical Input: Cuts pesticide use by 30–50%.
- Dual Functionality: Immune stimulation by 5-ALA + virus-targeting agents.
- Mitigates Phytotoxicity: Growth-promoting effects offset negative impact of chemical agents.
Application Tips and Optimization
1. Timing and Dosage
- Best applied preventively or at early infection stages.
- Adjust concentration based on crop (e.g., 50 mg/L 5-ALA + 500x Ningnanmycin dilution).
2. Environmental and Formulation Fit
- Avoid application under strong sunlight or high temperatures.
- Use compatible formulations (e.g., nano-emulsions) to improve stability.
3. Safety Considerations
- Monitor residue levels to ensure food safety.
- Assess effects on pollinators and soil microbes.
Future Development Directions
- Data-Driven Formulations: Build a virus-crop-specific synergy database.
- Smart Delivery Systems: Develop pH- or enzyme-triggered nano-carriers.
- AI Field Modeling: Use big data to optimize efficacy across environments.
5-ALA offers a promising approach for virus management in crops through its dual action—immune activation and direct viral inhibition. When integrated with antiviral agents, it enhances efficacy while supporting green agriculture goals. With advancements in formulation and digital agriculture, 5-ALA-based strategies are set to play a vital role in future plant protection systems.
