Call: HORIZON-HLTH-2024-DISEASE-08

Project: 101191666 — DEFENDER

The COVID-19 pandemic, caused by SARS-CoV-2, highlighted the threat posed by (re-) emerging viruses and mandates increased pandemic preparedness. Yet, predicting the next pandemic and its causative agent is challenging, given the existence of numerous pathogens, some unidentified, with significant harmful potential. These have been designated as high-priority (re-) emerging viruses by the World Health Organization (WHO), most lacking approved vaccines or treatments. Global strategies for viral infection prevention and control primarily rely on vaccination and antiviral drugs. It is therefore imperative to develop first-in-class and/or alternative antiviral approaches to strengthen the resilience of healthcare systems in the EU and globally, in anticipation of future pandemics.

Our newly EU-funded consortium DEFENDER aims to systematically address this pressing and unmet need, by adopting a comprehensive and integrative platform approach moving beyond virus-centric or single-gene methodologies, and applicable to a wide range of (re-) emerging viruses. DEFENDER’s revolutionary Research and Innovation (R&I) pipeline will focus on preventing virus entry through (i) a host bottom-up functional genetic approach in parallel to (ii) a virus top-down glycoprotein-centered approach. On the host side (i), we will identify novel virus entry factors, including attachment factors and proteins involved in endosomal uptake and virus genome uncoating, while on the virus side (ii), we will use virus glycoproteins to identify novel epitopes and broadly neutralizing nanobodies that block virus attachment and membrane fusion. By combining these approaches, DEFENDER will systematically identify and characterize novel vulnerable virus-host interaction sites laying the groundwork for new antivirals and immunogens.

In conclusion, with DEFENDER we have initiated a unique consortium which will generate novel and precise insights into virus-host interactions and molecular targets for intervention, which will feed into novel concepts for the development of next generation antivirals and immunogens.