On 31 January 2025, the third and final project period of the VIROFIGHT project officially concluded, marking the successful completion of the project.

We are pleased to share the final project summary, which highlights the key achievements and the broader impact of the research conducted over the course of the project.

Summary of the context and overall objectives of the project

Viruses pose a major threat to human health and society, causing widespread infections that lead to suffering and significant financial burdens. Many of the viruses listed by the World Health Organization (WHO) still lack effective treatments, and available antiviral drugs often require earlystage administration to be effective. In response, the VIROFIGHT project pioneered a revolutionary antiviral strategy by developing synthetic nano-shells designed to capture and neutralize entire viruses. Unlike conventional antivirals that target specific viral proteins or enzymes, this approach provided a broad-spectrum solution against multiple viral pathogens. To achieve this goal, the VIROFIGHT consortium integrated expertise from supramolecular chemistry, molecular nanoengineering, and virology. The project’s primary objectives included:
• Developing pre-assembled nano-shells capable of recognizing and engulfing viral particles.
• Engineering self-assembling molecular shells that polymerize on viral surfaces, preventing host cell interactions.
• Exploring RNA aptamers and protein-based molecular binders for virus-specific targeting.
• Validating these technologies through neutralization assays and preparing for potential in vivo testing.

This novel antiviral strategy aimed to provide broadly applicable antiviral treatments, reduce the scale and impact of viral infections, and contribute to global pandemic preparedness.

Work performed from the beginning of the project to the end of the period 

The VIROFIGHT project pursued two complementary approaches to virus neutralization:

Pre-Assembled DNA Origami Nano-Shells
Using DNA origami technology, the consortium successfully fabricated size-adaptable nano-shells capable of encapsulating viruses. These structures ranged from 40 nm to 280 nm, making them suitable for trapping most spherical human viruses. Functionalization with heparan sulfates (HS) further enhanced their virus-binding capabilities, enabling the trapping of up to ten different viruses and virus-like particles (VLPs) from various families. These results were confirmed through negative stain TEM and cryo-electron microscopy (cryo-EM). Additionally, antibody-functionalized nano-shells were tested for their ability to capture and neutralize specific viral targets. Notably, DNA shells decorated with anti-hepatitis B virus (HBV) antibodies demonstrated enhanced virus-blocking efficiency, surpassing the neutralization potential of free antibodies.

Self-Assembling Molecular Shells
The second approach focused on virus-triggered polymerization, where molecular building blocks assembled into virus-neutralizing structures on the viral surface. The team developed:
• Protein scaffolds inspired by natural immune defense mechanisms.
• De novo protein-based viral binders, designed to target viral glycosylation patterns.
• Oligomerized neutralizers, which demonstrated potent inhibition of Influenza, HIV, and SARSCoV-2 in nanomolar concentration ranges.
These self-assembling shells effectively prevented viral interaction with host cells, reducing viral infectivity.

Aptamer-Based Molecular Binders
To enhance virus targeting, the consortium developed RNA aptamers, which serve as high-affinity virus binders.
The team successfully: Established an aptamer selection pipeline to generate strain-specific and strain-insensitive aptamers. Developed high-affinity RNA aptamers against the SARS-CoV-2 spike protein. Integrated aptamers into nano-shells, demonstrating their potential as “molecular glue” for trapping viruses. However, challenges remained in identifying universal aptamers that bind across multiple virus strains.

Neutralization Assays and In Vitro Validation
The project validated its nano-shells and protein-based neutralizers through live-virus neutralization assays in in vitro assays with human cell lines using:
• Hepatitis B virus (HBV)
• Adenoviruses
• SARS-CoV-2
• Influenza virus
Results confirmed that DNA origami nano-shells functionalized with antibodies enhanced neutralization efficiency beyond that of free antibodies. Protein-based Griffithsin derivatives also showed strong inhibition against Influenza and HIV-1 pseudotypes, further supporting the potential of this approach. A spin-off company was established that obtained additional funding, allowing to further advance the technology and testing compounds in animals.

Progress beyond the state of the art, expected results until the end of the project and potential impacts

The VIROFIGHT project represents a breakthrough in antiviral technology, offering a paradigm shift in how viral infections are treated. Unlike traditional antivirals that target specific proteins or viral replication mechanisms, VIROFIGHT’s nano-shells provide a broadly applicable, modular approach to neutralizing diverse viral pathogens. Progress Beyond the State of the Art.

Key scientific advancements include:
• First-of-its-kind virus-engulfing nano-shells, engineered using DNA origami and protein design, with demonstrated effectiveness in trapping and neutralizing multiple virus families.
• Protein-based viral inhibitors, leveraging engineered oligomeric binders, such as Griffithsin derivatives, which exhibited broad-spectrum neutralization against Influenza, HIV, and SARS-CoV-2.
• High-affinity aptamer selection pipeline, successfully applied to SARS-CoV-2 spike proteins, opening the possibility of rapid aptamer discovery for new viruses.
• Enhanced neutralization efficiency of antibody-functionalized nano-shells, demonstrating improved performance over free antibodies in HBV and adenovirus models.

Potential Impacts and Socio-Economic Benefits
The impact of VIROFIGHT extends far beyond the laboratory, with significant societal, economic, and technological implications:
• Public Health and Pandemic Preparedness: The technology could be deployed as a universal antiviral platform, capable of neutralizing newly emerging viruses, potentially mitigating future pandemics.
• Cost Reduction in Healthcare: By providing a broad-spectrum solution, VIROFIGHT could reduce reliance on expensive virus-specific treatments, lowering healthcare costs.
• Biotechnology and Industrial Innovation: The project contributed to the European technology industry, leading to multiple patent filings and the foundation of a spin-off company focused on further development.
• Environmental and Food Safety Applications: Beyond medical applications, nano-shell technology could be adapted to purify water and food from viral contaminants, providing additional public health benefits.

Conclusion
The VIROFIGHT project successfully developed and validated nano-shell-based antiviral strategies that could redefine how viral infections are treated. The project has demonstrated remarkable scientific progress, with broad potential applications in medicine, pandemic preparedness, and biotechnology. VIROFIGHT represents a pioneering step toward universal antiviral treatments, with the promise of long-term societal impact and commercial viability.

For this year’s VIROFIGHT General Assembly we have chosen beautiful Slovenia.
Although Prof. Roman Jerala and his team are based in the capital Ljubiljana, he proposed to hold our annual meeting in Bled, a town near the Austrian border known for its beautiful scenery near mountains and a glacial lake.

We started the meeting on Tuesday afternoon, 13 June 2023, with an informal welcome coffee in the backyard of our meeting venue Villa Plemjava. After everyone had arrived, we started the meeting with the administrative part on project management and recent work on dissemination, communication and exploitation. There were indeed several seminal topics to discuss, but as unfortunately not all GA members could attend, we had to postpone decisions to a later date. Nevertheless, it was a fruitful discussion and after the end of the two presentations we headed for our last agenda item on day 1: the project consortium dinner at Bled Castle.
The castle is beautifully situated on top of a hill and already during the walk we could guess the beautiful view you will have when you finally reach the castle. We enjoyed a great dinner in a very cosy atmosphere and the consortium could exchange scientific ideas but also beyond.

The next day we started early in the morning with the scientific presentations and updates on DNAorigami nanoshell design, coiled-coil protein origami, aptamer functionality and neutralisation assays. All participants contributed with their best practices and ideas to solve experimental challenges, and an exchange of samples and materials was organised. Overall, the sessions were very interesting and it was good to meet face-to-face again and have lively discussions about the current project topics. As far as the schedule is concerned, the VIROIFGHT project is on track, even though the preparations for the animal experiments will take some time, but these important and necessary experiments will start soon.

After a general summary and summing up words from our Coordinator Hendrik Dietz, we ended the meeting with lunch at the nearby Hotel Rose. Afterwards, everyone went home with fond memories of Bled and exciting new tasks for the project.

We would like to thank everyone for attending this General Assembly, but especially Roman Jerala and Martina Mohorčič from NIC for the warm welcome and perfect organisation of this meeting.