In collaboration with 12 partners from 6 countries, BioQuant’s High Content Analysis of the Cell (HiCell) research group is establishing the Antivirus Pandemic Preparedness EuropeAn pLatform (APPEAL), a European research initiative aimed at enhancing preparedness for future pandemics. This EU-funded collaboration will establish a comprehensive program for the development of broad-spectrum antiviral drugs within a five-year timeframe ensuring drug affordability and accessibility to low-income countries.

The COVID-19 pandemic has highlighted the profound impact of the emergence of dangerous viruses. While the World Health Organization identifies Ebola, Lassa, and Zika viruses as pathogens that present a particularly high risk for future epidemics or pandemics, it is important to note that the Influenza virus, despite not being included in this list, has demonstrated the potential to cause significant harm on multiple occasions throughout the 20th and 21st centuries.

Vaccinations and antiviral drugs are fundamental components of global pandemic preparedness, playing a crucial role in preventing and mitigating the impact of infectious diseases. However, these measures require continuous adaptation due to the genetic variability of viruses. This is a costly and time-delayed burden for each outbreak. To mitigate this, the APPEAL project will focus on identifying and targeting less variable mechanisms within infected cells that are essential for viral replication, as well as the immune processes through which host cells defend against viral infections.

The consortium led by Jena University Hospital is prioritising the identification of antiviral agents that target host cell proteins. This approach significantly reduces the risk of resistance development and enhancing the long-term effectiveness of the antiviral agents.

Searching for agents in silico, in vitro, and in vivo
The APPEAL project aims to establish a platform for the identification of target proteins and their associated signalling pathways within host cells, by utilising both computational and experimental approaches. 

The proposed comprehensive workflow commences with the mining of published data from high-throughput gene knockout studies with infected cells, followed by computational analysis using machine learning and experimental approaches. This will result in a list of proteins and pathways expected to impact the host cells’ antiviral response.

The HiCell group, headed by Holger Erfle, will provide their expertise and technology for the high-content screening of these potential drug targets. Their High-Density Cell Arrays (HD-CA) will be employed and further developed to not only identify proteins and cellular processes essential to the viral life cycle by gene knockout, but also proteins that could act as enhancers of cellular defence mechanisms by targeted gene activation.

Subsequently, identified proteins will be further investigated and experimentally validated in infected human primary cells and physiologically relevant 3D-human tissue models. Promising candidates will then advance to pre-clinical studies, and ultimately, validation in clinical pilot study.
The scientists are optimistic that at least one substance can go through these steps in a fast-track procedure, to be validated during the project’s duration.

The project funded with a total budget of 8.1 million Euro by the EU with the participation of Great Britain, is coordinated by Heidelberg University alumnus Prof. Rainer König, now head of the ‘Systems Biology’ research group at Jena University Hospital. König summarises the objective of the project as:

[The APPEAL] pipeline is intended to respond quickly, safely and effectively to the spread of new or re-emerging dangerous viral infections.

Find more information on the project's website

Participating institutions in the APPEAL project:

• Jena University Hospital, Germany
• Johann-Wolfgang-Goethe University, Frankfurt, Germany
• Imperial College London, UK
• Ruprecht-Karls-University Heidelberg, Germany
• Greifswald University Medicine, Germany
• Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Infectiologie de Montpellier, France
• ERINHA European Research Infrastructure on Highly Pathogenic Agents, Brussels, Belgium
• Erasmus Medical Center, Rotterdam, The Netherlands
• Institut Pasteur, Paris, France
• ECRIN European Clinical Research Infrastructure, Paris, France
• MatTek in vitro Life Science Laboratories, Bratislava, Slovakia
• Welab Barcelona (Acondicionamiento Tarrasense Associacion) Spain
• ConsulTech Technologieberatung GmbH, Berlin, Germany

The APPEAL project has received funding from the European Union's Horizon Europe research and innovation programme under Grant Agreement No 101137311. 
HORIZON-HLTH-2023-DISEASE-03-04: Pandemic preparedness and response: Broad spectrum anti-viral therapeutics for infectious diseases with epidemic potential

Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or European Commission. Neither the European Union nor the granting authority can be held responsible for them.