Harnessing RNAi and Nature's Arsenal
Innovative Strategies Against Viral Diseases
The future of antiviral therapy may lie in our ability to harness our own cellular machinery and nature's hidden resources.
The Evolving Battle Against Viruses
Infectious diseases present moving targets for researchers—their ability to mutate, hide within our cells, and develop resistance demands constant innovation. The remarkable progress in HIV treatment, transforming what was once a fatal diagnosis into a manageable chronic condition, demonstrates what focused scientific effort can achieve.
600,000+
HIV deaths in 2022
1.3 Million
New HIV infections in 2022
40 Million
People living with HIV worldwide
3x Risk
HSV-2 increases HIV acquisition
Key Challenges
- Viral reservoirs allow HIV to hide dormant in cells, preventing complete eradication
- Rapid mutation rates create diverse viral strains that evade both natural immunity and conventional vaccines
- Growing antimicrobial resistance threatens our ability to treat common infections
Silencing Viruses: A Revolutionary Approach to Antiviral Therapy
One of the most promising strategies presented at the symposium came from researchers exploring RNA interference (RNAi) as an antiviral weapon. RNAi represents a natural cellular process that cells use to silence specific genes, and scientists have learned to harness this mechanism to target viral pathogens.
The siRNA Design Breakthrough
Showkat Ahmad Dar and Manoj Kumar from Virology Discovery Unit and Bioinformatics Centre in Chandigarh developed an innovative method for designing and testing chemically modified siRNA (small interfering RNA) against dengue virus 1 .
Computational Design
Using virus-specific algorithms (VIRsiRNApred and SMEpred) to design siRNAs targeting different regions of the dengue virus genome
Chemical Modification
Adding deoxy-nucleotides to the two 3' overhangs of the siRNA to enhance stability
Efficacy Testing
Cloning target genes into specialized plasmids and using dual luciferase assays to measure knockdown efficacy
Toxicity Assessment
Employing MTT assays to ensure the designed siRNAs were not harmful to human cells
Research Outcomes
The results were impressive—the designed siRNAs performed according to their prediction efficacies, successfully silencing their target genes without showing significant toxicity to human cells 1 .
siRNA Development Process
Computational Design
Algorithm-based siRNA selection
Chemical Modification
Enhanced stability
Efficacy Testing
Luciferase assays
Toxicity Assessment
MTT assays
Nature's Pharmacy: Marine Compounds Against Viral Infections
While some researchers focused on designing synthetic molecules, others looked to the natural world for inspiration. The oceans, which cover most of our planet, contain a vast array of organisms producing unique chemical compounds with potential therapeutic applications.
Marine Algae Against HSV-2
A team from Sathyabama Institute of Science and Technology in Chennai investigated marine brown algal compounds as potential inhibitors of Herpes Simplex Virus-2 (HSV-2), the primary cause of genital herpes 1 .
This research is particularly important because HSV-2 infections increase the risk of acquiring HIV approximately threefold, creating a dangerous synergy between these viral infections.
Sargassum species of marine algae being studied for antiviral properties
Immune-Boosting Marine Compounds
In related research, the same team explored the potential of marine extracts to stimulate cytokine production and anti-tumor activity. They discovered that certain aqueous extracts and purified compounds from marine algae significantly stimulated IL-2 and IL-21 cytokines in human PBMCs (peripheral blood mononuclear cells) 4 .
| Compound/Extract | Biological Effect | Potential Therapeutic Application |
|---|---|---|
| Aqueous algal extracts | Significant stimulation of IL-2 and IL-21 | Cancer immunotherapy, immune enhancement |
| Compound 1 | Significant stimulation of IL-2 and IL-21 | Cancer immunotherapy, immune enhancement |
| Compound 2 | Significant stimulation of IL-2 and IL-21 | Cancer immunotherapy, immune enhancement |
| All tested extracts | No toxicity up to 10 mg/ml | Favorable safety profile for future development |
IL-21 is particularly valuable therapeutically as it is a potent stimulator of T cell anti-tumor immunity. The researchers noted that the structural identification of the cytokine-stimulating principle compounds was still underway, suggesting that the most exciting discoveries might still be ahead 4 .
The Scientist's Toolkit: Essential Research Reagents and Methods
Modern infectious disease research relies on sophisticated tools and techniques. The studies presented at ISSHID 2019 utilized a diverse array of laboratory methods and reagents to advance our understanding of viral infections and potential treatments.
| Research Tool | Specific Application | Function in Research |
|---|---|---|
| CRISPR-Cas9 system | HIV proviral DNA excision | Gene editing to remove integrated viral DNA |
| VITEK-2 system | Bacterial identification | Automated identification of exotic bacterial pathogens |
| CRISPR-attack system | Targeting HIV reservoirs | Combinatorial approach to target HIV in various hiding places |
| Histopaque | PBMC isolation | Separating specific immune cells from blood samples |
| Cytokine bead array | Multiplex cytokine detection | Measuring multiple immune signaling molecules simultaneously |
| Dual luciferase assay | siRNA efficacy testing | Quantifying gene silencing effectiveness |
| MTT assay | Toxicity testing | Measuring cell viability and compound safety |
| Adeno-associated virus vectors | Antibody delivery | Long-term expression of therapeutic antibodies |
CRISPR-Cas Applications
The CRISPR-Cas system has emerged as a particularly powerful tool, with researchers at Amsterdam UMC developing "a robust and safe combinatorial CRISPR-Cas regimen" that can "inactivate diverse HIV strains across various cellular contexts" .
AAV Vector Delivery
Similarly, adeno-associated virus (AAV) vectors have shown promise as delivery vehicles for antiviral therapies. Researchers have used AAV to enable long-term expression of therapeutic proteins like eCD4-Ig 2 .
The Future of Infectious Disease Research
As we look ahead, several promising avenues emerge from the research presented at ISSHID 2019. The combination of computational design and experimental validation represents a powerful paradigm for accelerating therapeutic development. Similarly, the exploration of natural products from marine and other environments continues to yield novel compounds with therapeutic potential.
Computational Design
Algorithm-driven therapeutic development
Natural Products
Marine and environmental compound exploration
Gene Editing
CRISPR-based therapeutic approaches
Perhaps most exciting is the convergence of different approaches—where gene editing technologies like CRISPR may be combined with long-acting antiretroviral therapies and immune-boosting compounds to create multifaceted attack strategies against persistent viral infections.
Researcher Perspective
As Dr. Elena Herrera-Carrillo and her team noted regarding their CRISPR-based approach to targeting HIV, "We have developed an efficient combinatorial CRISPR-attack on the HIV virus in various cells and the locations where it can be hidden in reservoirs." However, they appropriately caution that while "these findings represent a pivotal advancement towards designing a cure strategy," we must still achieve "the right balance between efficacy and safety" before considering clinical trials in humans .
Conclusion
The research presented at ISSHID 2019 reflects an evolving landscape in infectious disease research—one that harnesses both cutting-edge technologies like CRISPR and RNAi alongside nature's own chemical diversity. These approaches, while distinct in their methodologies, share a common goal: to develop more effective, targeted strategies against pathogens that have long plagued humanity.
As these technologies mature and converge, we move closer to a future where today's incurable infections become manageable, and where the constant threat of emerging pathogens can be met with rapid, targeted countermeasures. The battle against infectious diseases continues, but with an increasingly sophisticated arsenal at our disposal.