Periodic Reporting for period 1 - NAVIPP (New AntiVirals for Infections with Pandemic Potential)
Reporting period: 2024-01-01 to 2025-06-30
The COVID-19 pandemic demonstrated the urgent need for antiviral medicines that can be deployed rapidly when new viruses emerge. While vaccines are a cornerstone of prevention, effective antivirals are essential to treat patients, reduce transmission, and provide a critical bridge while vaccines are being developed. However, the global therapeutic arsenal against emerging viruses remains very limited.
The NAVIPP project (“New Antivirals for Infections with Pandemic Potential”) was launched in January 2024 to address this gap. Bringing together leading European research infrastructures, academic centres, industry partners and SMEs, NAVIPP aims to create a robust platform for the discovery, validation, and clinical testing of broad-spectrum antivirals (BSAVs). The project focuses on highly pathogenic viruses with epidemic or pandemic potential, including filoviruses (such as Ebola), flaviviruses (such as dengue and Zika), coronaviruses, and henipaviruses.
Its overall objectives are:
1. To identify novel antiviral molecules with activity against multiple viral families with pandemic potential.
2. To establish innovative preclinical models and a responsible roadmap for in vivo validation.
3. To determine the mode of action of promising antivirals.
4. To develop the framework for an adaptive platform trial for early clinical evaluation.
5. To facilitate the long-term implementation of BSAVs in public health preparedness.
By integrating discovery, translational research, and clinical readiness, NAVIPP supports the EU’s strategy for pandemic preparedness and contributes to global health security.
The NAVIPP project (“New Antivirals for Infections with Pandemic Potential”) was launched in January 2024 to address this gap. Bringing together leading European research infrastructures, academic centres, industry partners and SMEs, NAVIPP aims to create a robust platform for the discovery, validation, and clinical testing of broad-spectrum antivirals (BSAVs). The project focuses on highly pathogenic viruses with epidemic or pandemic potential, including filoviruses (such as Ebola), flaviviruses (such as dengue and Zika), coronaviruses, and henipaviruses.
Its overall objectives are:
1. To identify novel antiviral molecules with activity against multiple viral families with pandemic potential.
2. To establish innovative preclinical models and a responsible roadmap for in vivo validation.
3. To determine the mode of action of promising antivirals.
4. To develop the framework for an adaptive platform trial for early clinical evaluation.
5. To facilitate the long-term implementation of BSAVs in public health preparedness.
By integrating discovery, translational research, and clinical readiness, NAVIPP supports the EU’s strategy for pandemic preparedness and contributes to global health security.
During the first 18 months, NAVIPP has made substantial progress across all work packages.
• Compound library and screening: A diverse library of over 300 000 molecules was built, surpassing the original target of 125 000. High-throughput screening campaigns were completed against four viral families (Filoviridae, Flaviviridae, Paramyxoviridae, Coronaviridae), yielding more than 160 promising hits. Early validation confirmed activity of 17 compounds against Ebola virus in BSL-4 laboratories.
• Ex vivo and in vitro validation: Human precision-cut lung slices (hPCLuS) were established and cryopreservation protocols optimised, enabling transfer to high-containment partners. Antiviral assays were validated for multiple priority viruses, and first hits are being confirmed.
• Preclinical evaluation: Preparatory work was completed for pharmacokinetics, safety studies and in vivo efficacy assays. Although experimental testing will take place in later phases, timelines remain on track.
• Mechanistic studies: Cell painting and proteomic platforms have been prepared to unravel how candidate antivirals act at the molecular level.
• Vectorisation and product profiles: Nanofitin®-based technologies were advanced to extend drug half-life and enable novel conjugation strategies. The consortium also supported WHO in developing Target Product Profiles for dengue and Nipah virus therapeutics.
• Clinical readiness: A major milestone was the design of the ADAPT platform trial for dengue. A retrospective analysis of over 2,300 dengue patients clarified links between viral load and severity, informing trial methodology. Protocols and approvals were secured in Vietnam (with Malaysia pending), logistics and risk monitoring plans finalised, and candidate therapeutics prioritised. Recruitment is expected to start in late 2025.
• Project management and communication: Governance structures were established, all due deliverables (Project Management Handbook, Data Management Plan, Dissemination & Communication strategy) were completed, and the project’s website launched.
• Compound library and screening: A diverse library of over 300 000 molecules was built, surpassing the original target of 125 000. High-throughput screening campaigns were completed against four viral families (Filoviridae, Flaviviridae, Paramyxoviridae, Coronaviridae), yielding more than 160 promising hits. Early validation confirmed activity of 17 compounds against Ebola virus in BSL-4 laboratories.
• Ex vivo and in vitro validation: Human precision-cut lung slices (hPCLuS) were established and cryopreservation protocols optimised, enabling transfer to high-containment partners. Antiviral assays were validated for multiple priority viruses, and first hits are being confirmed.
• Preclinical evaluation: Preparatory work was completed for pharmacokinetics, safety studies and in vivo efficacy assays. Although experimental testing will take place in later phases, timelines remain on track.
• Mechanistic studies: Cell painting and proteomic platforms have been prepared to unravel how candidate antivirals act at the molecular level.
• Vectorisation and product profiles: Nanofitin®-based technologies were advanced to extend drug half-life and enable novel conjugation strategies. The consortium also supported WHO in developing Target Product Profiles for dengue and Nipah virus therapeutics.
• Clinical readiness: A major milestone was the design of the ADAPT platform trial for dengue. A retrospective analysis of over 2,300 dengue patients clarified links between viral load and severity, informing trial methodology. Protocols and approvals were secured in Vietnam (with Malaysia pending), logistics and risk monitoring plans finalised, and candidate therapeutics prioritised. Recruitment is expected to start in late 2025.
• Project management and communication: Governance structures were established, all due deliverables (Project Management Handbook, Data Management Plan, Dissemination & Communication strategy) were completed, and the project’s website launched.
NAVIPP already demonstrates advances that go beyond current antiviral R&D practice:
• Scale of discovery: By screening more than 300,000 molecules, the project has broadened the chemical space available for pandemic antivirals, increasing the likelihood of identifying truly novel chemotypes.
• Innovative models: The establishment of hPCLuS ex vivo systems and their cryopreserved transferability represent a breakthrough in physiologically relevant, sharable models for high-containment pathogens.
• Adaptive trial design: The ADAPT platform creates a reusable clinical infrastructure, reducing time to evidence generation when future outbreaks occur.
• Vectorisation technologies: Progress on Nanofitin® half-life extension offers a novel route to make antivirals more clinically viable.
Looking ahead, the project will focus on mode-of-action studies, in vivo validation, and the translation of laboratory hits into trial-ready candidates. Wider uptake will require continued engagement with regulators, industry, and global health organisations to ensure that promising BSAVs progress into development pipelines.
• Scale of discovery: By screening more than 300,000 molecules, the project has broadened the chemical space available for pandemic antivirals, increasing the likelihood of identifying truly novel chemotypes.
• Innovative models: The establishment of hPCLuS ex vivo systems and their cryopreserved transferability represent a breakthrough in physiologically relevant, sharable models for high-containment pathogens.
• Adaptive trial design: The ADAPT platform creates a reusable clinical infrastructure, reducing time to evidence generation when future outbreaks occur.
• Vectorisation technologies: Progress on Nanofitin® half-life extension offers a novel route to make antivirals more clinically viable.
Looking ahead, the project will focus on mode-of-action studies, in vivo validation, and the translation of laboratory hits into trial-ready candidates. Wider uptake will require continued engagement with regulators, industry, and global health organisations to ensure that promising BSAVs progress into development pipelines.