For infectious disease management and control, vaccines are considered golden countermeasures. but are not the most adequate tool for mitigating the early effects of an outbreak. Taking the recent COVID-19 pandemic as an example, access to broadly applicable therapeutic antivirals would have had a major impact, decreasing the human toll of the disease, and alleviating the burden carried by health care systems. It is urgent to focus resources and efforts on the development of broad spectrum antiviral drugs against unknown pathogens. The NAVIPP consortium aims to strengthen the EU’s readiness and response capacity to viral threats by assembling an international R&D platform for antiviral drug development against pandemic prone pathogens. The consortium will implement a strategic, multi gear R&D and clinical roadmap for the identification, optimisation, preclinical and clinical investigation of broad spectrum antivirals against pathogens with epidemic or pandemic potential. In particular, the consortium will design compounds library with increased diversity to be tested in high-throughput assays against highly pathogenic viruses. Hits coming from this exercise, as well as assets that have demonstrated antiviral activity in previous exercises, will be assessed against a larger virus panel. Validation of the antiviral efficacy of the hits will be done in state-of-the art ex vivo models to prioritize compounds going to in vivo proof of concept studies. Mode of action and target will be also interrogated. Additionally, the implementation of an adaptive platform trial will enable early clinical investigation of 3 antivirals and will pave the way for clinical testing of other antivirals. Finally, the project will investigate new innovative and improved delivery systems of antivirals through nano conjugation. Ultimately, this project will deliver a pipeline of broad-spectrum anti-viral candidates and in the longer term contribute to European preparedness for emerging threats.

Developing new antiviral treatment against viruses and particularly high-priority emerging and re-emerging viruses as listed by the WHO, remains crucial as, among other aspects, the viruses evolve under selection. Broad spectrum host-directed antiviral drugs (HDA) are promising therapeutic options, however the robust identification of relevant host factors by genome-wide knockout screens is challenging due to low consistency in the resulting hits. Our project aims to (1) establish a computational and experimental pipeline to identify and validate an antiviral for these viruses, and (2) identify at least one broad spectrum antiviral drug against potential emerging and re-emerging viruses as listed by the WHO. To address these, we will implement a drug selection pipeline following several strategies: We will employ (i) machine learning, based on data from knockout screens, proteomics, protein interaction, transcriptomics of infected cells with pandemic-related viruses, Genome-Wide Association Studies, and generic gene descriptors, (ii) High Density Cell Arrays, which provide much more detailed readouts compared to state of the art pooled knockout screens, (iii) primary cell cultures obtained from a diverse array of human tissues, as they are more appropriate to study the host cell physiology during infection, compared to cancer cell lines, and (iv) use the pipeline to identify host restriction factors, which, when activated, challenge the virus; followed by innovative drug development and delivery based on small activating RNA. The pipeline comprises an Expedited Arm for which broad spectrum antiviral drugs for repurposing will be selected followed by in vitro and in vivo efficacy testing, and a clinical trial as a proof of concept. The elaborated Arm includes all strategies (i)-(iv) and will provide a sustainable pandemic preparedness pipeline ready-to-operate to identify the appropriate treatment against the emerging virus at the early time of a new outbreak.

COVID-19 has highlighted the need for EU preparedness towards the growing number of virus outbreaks. Research infrastructures are strategic tools for providing resources and access to technologies for research, promoting innovation and supporting public health actions, but their impact is limited when they operate individually. The European Viral Outbreak Research Alliance (EVORA) project brings together three RIs (EVA, ERINHA-ESFRI and ELIXIR-ESFRI) with unique and complementary expertise in bio-banking, high containment facilities and data management solutions, respectively, under a single concerted interoperable framework with a common and long-term perspective. EVORA aims to strengthen EU capacity for concerted preparedness and response to viral diseases, unify RI operations to achieve optimal RI responsiveness, sustainability and worldwide competitiveness and address specific regulatory, ethical, and security challenges related to emerging pathogens. EVORA will create synergies between the RIs through common governance and concerted decision-making mechanisms. The interoperability of EVORA services will be integrated, through unified operational procedures and quality standards, in order to support user needs and EU Health-Tech in either “inter-crisis” or “viral emergence response” conditions. Finally, the project will address the complex regulatory aspects of preclinical research involving high-risk pathogens, to ensure the operability of the structure. By paving the way for a sustainable alliance of state-of-the-art RIs for preparedness and response to viral emergence, EVORA will strengthen the cohesiveness of the RI landscape in the field, contribute to the competitiveness of the European Research Area (ERA), and ultimately improve the EU's resilience to emerging communicable diseases.

The CCHFVACIM project is an ambitious collaborative effort aimed at developing both prophylactic and therapeutic effective countermeasures against Crimean Congo Haemorrhagic Fever Virus (CCHFV), one of the most threatening vector-borne pathogens, widely distributed, including in the European continent. Deep structural biology studies on viral glycoproteins and investigation of the immunogenicity of the viral antigens will be combined with optimisation of an mRNA vaccine candidate against the virus and characterisation of the resulting protective immunity, as well as with the development of immunotherapeutic monoclonal antibodies (mAbs) based on CCHFVs antigenic targets. To achieve the overarching goals, the CCHFVACIM project will build on the success of previous projects such as CCHFever (FP7), CCHFVaccine (H2020) and go the extra mile by initiating a unique One-Health platform strategy to address different aspects of this severe public health threat. On one hand, the project will use several advanced animal models (mice, sheep, and non-human primate) to assess and compare the efficacy of mRNA vaccine candidates, mAbs and therapeutic mRNA; on the other hand, it will establish a biobank from CCHF patients to build up a pipeline for the production of mAbs against CCHFV from their B cells. Importantly, the project will also contribute to capacity building of European infrastructures, with the establishment of a platform on mRNA-based vaccine at one of the partner institutions. Ultimately, CCHFVACIM will permit to develop a road map to bring the most efficacious vaccine candidates and immunotherapy tools to clinical trial Phase I in humans. The project results will be widely disseminated among the scientific community, public health authorities, non-governmental organisations, outbreak management teams, and hospitals, with the final scope of both contributing to contain the burden of CCHF disease and increasing preparedness to new outbreaks.

Infectious diseases (ID) pose a continuous and serious threat to global health and economies. Reducing the impact of emerging infectious diseases (EID) and antimicrobial resistance (AMR) requires long-term, sustainable, international efforts. The European consortia COMBACTE and PREPARE have the joint ambition to establish a coordinated, permanent, pan-European infrastructure for clinical research on ID (ECRAID). The mission of ECRAID is to reduce the impact of ID on individual and population health by generating rigorous evidence to improve the diagnosis, prevention and treatment of IDs, and to better respond to ID threats. In ECRAID-Plan the coordinators and co-coordinators of PREPARE and COMBACTE, together with the (co-)coordinators of 12 other highly complementary networks and infrastructures, will develop a detailed Business Plan for ECRAID, which will serve: (i) as the guiding document in the implementation of ECRAID, (ii) to inform external stakeholders (network partners, industry, funders, policy makers, regulators, users) about ECRAID and (iii) to get commitment for sufficient start-up funding to commence operations in ECRAID, allowing for a smooth transition of activities from the current funding periods of PREPARE and COMBACTE. ECRAID-Plan will be completed within 24 months, involving extensive consultation of a multisectoral stakeholder platform. ECRAID-Plan will focus on the development of the key components of the business plan, including (i) an internal analysis of strengths and weaknesses, (ii) an external analysis of relevant stakeholders and their needs, developments in the scientific, policy and other domains and opportunities and threats, (iii) the service offering and business model, (iv) operational processes and policies, (v) governance structure and (vi) an investment plan and operational budget. Cross-cutting themes include reconciliation of AMR and EID research, data sharing and interoperabilty of networks.