13 exceptional partners from 6 countries form the APPEAL consortium

This consortium bundles strong expertise in virology (GUF, CNRS, IP, EMC), genome-wide and secondary, bidirectional CRISPR screening (CNRS), microscopy-based RNAi and CRISPR/Cas screening technology (UHEI), Human tissue models (MatTek), bioinformatics/machine learning (JUH, UMG), and two ESFRI landmarks: ERINHA, the European Research Infrastructure on Highly pathogenic agents (ERINHA), which specialises in the study of high-consequence infectious agents and high-containment research, and ECRIN, the European Clinical Research Infrastructure Network, for the coordination of clinical studies. Project management as well as dissemination and exploitation activities are delivered by CT.

The coordination institution is the Jena University Hospital (JUH), Germany. Prof. Dr Rainer König is professor and research group leader of the Institute of Infectious Diseases and Infection Control, which is a leading player in various funding programs and consortia, such as Center for Sepsis Control and Care, InfectControl 2020, and others. He has established several machine learning pipelines to identify essential genes in a variety of organisms and for different applications. His expertise suits perfectly to construct and apply the prioritisation pipeline for HDF/HRF selection in WP 1, and to select drug targets using machine learning and network modelling to identify efficient treatment combinations in WP 4. More information about his group is found here.	The research group of Dr. med. Tuna Toptan Grabmair (Johann-Wolfgang-Goethe Universität Frankfurt am Main, GUF) seeks to identify host and viral factors essential for the pathogenesis of pandemic-related RNA virus infections as well as human tumor virus-associated cancers. They use in vitro infectious model systems and recombinant viruses to study the pathogenesis of corona and influenza virus infections among others using conventional and omics-based analysis. Her expertise in high-throughput screening and functional analysis using different virus and cell culture models qualifies her group to perform broad spectrum screens in WP 3 and in vitro analysis of the selected compounds in WP 5. Her institute is well-equipped to perform planned experiments in BSL-2 and BSL-3, and is strongly connected with European partners working on SARS-CoV-2 therapy, such as the German Centre for Infection Research (DZIF), the National Pandemic Cohort Network (NAPKON), Clusterproject ENABLE, Pandemie Network Hessen, LOEWE Consortium CoroPAN and the Fraunhofer Institute for Translational Medicine and Pharmacology.	The Advanced Biological Screening Facility (ABSF) and the research group HiCell in BioQuant run by Holger Erfle at the at the Ruprechts-Karls-Universität Heidelberg (UHEI) co-develops assays for RNAi screening and provides automated sample preparation, high-throughput, high-content microscopy-based screening and a data analysis pipeline. The Facility developed a unique cell-based screening platform - High-Density Cell Arrays (HD-CA) - which allows for parallel cellular analysis of more than 24.576 samples (256 x 96-well plates) in one experiment. HD-CA are of special importance in WP 2 and 3. The developments will facilitate the screen for HDF/HRF of diverse viral systems. UHEI developed automated image and data analysis pipelines for classification of the resulting phenotypes based on their work conducted in the analysis for virus-host interaction screens in the ImmunoQuant and ViroQuant consortia. The ABSF was involved in several RNAi screens for the dissection of virus–host interactions and the identification of drug targets for diverse viruses including HIV, AAV and HCV in the past.
The Institute of Bioinformatics at the Universitätsmedizin Greifswald (UMG), headed by Prof. Lars Kaderali, specialises in bioinformatics applications in virology. Lars Kaderali is well known for his expertise in modelling virus-host interactions. His group has developed computational models describing the intracellular replication of a range of different RNA viruses, and they have used these models to identify in silico optimal antiviral strategies. Furthermore, Prof. Kaderali has extensive experience in analysing siRNA screening data. His group has developed RNAither, one of the major statistical pipelines available for siRNA screening data analysis, which has been applied to a large number of viral screens to identify HDF and HRF. This method will be used in WP 4 for the analysis of HD-CA data. UMG has developed statistical approaches to normalize siRNA screening data for cell populations, as well as approaches for meta-analysis and host factor priorization. Prof. Kaderali is member of the expert panel of the federal chancellor of Germany on COVID-19, and advises the federal government as well as the state government of Mecklenburg-Vorpommern on pandemic responses and pandemic preparedness. More about his group here.	CNRS - Centre national de la recherché scientifique Caroline Goujon’s research group, named Interferon and antiviral restriction lab, has been established in January 2015 at the CNRS institute of research on infection of Montpellier (IRIM). It aims at identifying novel cellular effectors of the interferon-induced antiviral state (using, among other approaches, genome-wide CRISPR screens) and at characterizing the molecular mechanisms involved in their antiviral activity. In APPEAL, Caroline Goujon's team will provide guidance and tools to Mathieu Matteo’s team in order for them to perform the genome wide screens in Nipah and Lassa virus infected cells (WP1, task 1.1). Caroline Goujon's team will participate in WP2 and help optimizing the HD-CA with CRISPR on different cell lines and viruses. The team will work on WP3 (all tasks) in close collaboration with the other 2 teams of molecular virologists, Mathieu Mateo’s and Tuna Toptan Grabmair’s, perform the HD-CA experiments in several cell lines and for several pathogenic viruses, the following pooled library validation screens as well as the arrayed screens in primary cells and epithelia provided by MaTtek partner. Caroline Goujon's team will be involved in WP5 (task 5.3) and study the in vitro efficacy testing of the drug candidates and study their mode of action.	The European Research Infrastructure on Highly pathogenic Agents (ERINHA) is a non-profit pan-European distributed research infrastructure dedicated to the study of highly pathogenic emerging and re-emerging agents. Its mission is to advance research on these pathogens, contribute to the development of medical countermeasures against them and ultimately increase preparedness and responsiveness to highly pathogenic infectious threats. ERINHA gathers the capacities and expertise of ten high and maximum containment (BSL-3 and BSL-4) laboratories throughout Europe. ERINHA has been a Landmark of the European Strategy Forum on Research Infrastructures (ESFRI) since 2018. The infrastructure will support the APPEAL consortium by providing in vivo capacities of one of its members, the Erasmus Medical Centre (EMC), a Europe- and world-leading research institution with world-known expertise in respiratory viruses, especially coronaviruses and influenza.
Mathieu Mateo belongs to an Institut Pasteur (IP) unit, UBIVE, hosted by the International Center of Infectiology in Lyon to have direct access to the INSERM P4 Jean Mérieux BSL-4 laboratory. IP is a research team but also hosts the National Reference Center for Viral Hemorrhagic Fever (NRCVHF), headed by Sylvain Baize. IP studies the biology of arenaviruses, their pathophysiology and immune responses. He has developed reverse genetics systems for arenaviruses, vaccines against arenaviruses with one of them passing phase I clinical trial and has participated in the validation of antiviral molecules. Through the NRCVHF, he has access to all known RG4 pathogens including Ebola, Lassa, Nipah or CCHFV, from laboratory strains to field strains collected during this missions.	ECRIN-ERIC is a European Research Infrastructure facilitating multinational clinical research, through the provision of advice and services for the set-up and management of investigator or SME led clinical studies in Europe. ECRIN unites national networks of clinical trial units across Europe, through its scientific partners, to fulfil its vision of generating scientific evidence to optimise medical practice. By supporting clinical trials across borders and advising and implementing policy, ECRIN advances knowledge flow, competitiveness and integration in European clinical research. Main tasks in the project: With its cross-border experience, acquired from both the provision of clinical trial services and participation in capacity building projects, and access to clinical research infrastructures, ECRIN will support the clinical study (WP7). Website: www.ecrin.org	For more than 25 years, Mattek in vitro life science laboratories SRO (MT) has been the world leader in reliable in vitro human tissue model innovation with physiologically relevant 3D models of skin, ocular, oral, respiratory, liver, kidney and intestinal tissue models. MT’s expertise in cell isolation and expansion allowed the development of high quality primary human cells and culture media for research in 2D and 3D. Produced from primary human cells using cutting edge tissue engineering technology, MatTek tissue models provide a microphysiological platform to model highly relevant and predictive human biology. During the COVID-19 pandemic, the global availability of respiratory tract tissues has allowed laboratories to study the mechanism of action of viruses, target identification, drug development and screening in human airway models. In the context of APPEAL, MatTek’s scientists Dr. Christian Pellevoisin, ERT, Dr. Seyoum Ayehudi and Dr. Jan Markus - experts in cell culture, tissue engineering, toxicology and method development - will provide relevant 2D and 3D experimental systems for the screening platforms in WP 3 and 5.
Welab (WL) is an integrated drug discovery and development platform. It was founded in 2020 after the acquisition of the R&D site of Esteve Pharmaceuticals. The team has experience of, on average, more than 15 years in pharmaceutical research, and a proven track record in drug discovery and development. Therefore, they have all the capabilities from target identification up to preclinical studies, including molecular modelling and virtual screening, medicinal and analytical chemistry, in vitro and in vivo pharmacology, drug metabolism and pharmacokinetics, and toxicology. WeLab is a certified GLP-compliant organisation as it regards to DMPK-Tox and analytical chemistry studies. Welab’s team has been involved in several IMI, and IMI2 projects, either as partners (e-TOX, Emtrain, Europain, IMI-Paincare) or in a leading role (NGN-PET). These projects covered broad areas of pharmaceutical research of animal models, in vitro and in vivo techniques, and clinical samples bioanalysis. WL will participate in the target selection (WP4), drug development and selection (WP5) and drug in vitro and in vivo testing (WP6).	Since its inception in 1992, the SME ConsulTech GmbH (CT) provides project management services for large research and innovation projects. The focus is on projects with a pharmaceutical, medical, medtec or biotechnology focus. CT supports the partners in administrative and scientific tasks and has been involved in a number of European projects, most importantly in the context of APPEAL is the IMI-PAINCARE project encompassing 40 partners. Here, CT was also co-managing and co-responsible for various aspects while the conduct of 6 clinical studies (ethics, monitoring, pharmacovigilance, regulatory, pre-clinical and clinical analytics). In addition, CT is the project management partner supporting the various administrative challenges that occur during the implementation of the project. Furthermore, CT leads the communication, dissemination and exploitation activities. Moreover, CT follows its own research agenda: to improve diagnostics and therapy for brain tumours. As such, CT is excellently positioned to facilitate and support the implementation of APPEAL through its project management (WP8), outreach (WP9) and clinical study expertise (WP7).	The translational research team at Imperial College London (ICL) are at the frontline of developing new and exciting therapeutic oligonucleotides (small activating RNA duplexes) in partnership with MiNA Therapeutics Ltd. The ICL team has a deep understanding of how to exploit the untranslated regulatory regions of any gene for their use in RNA drug development. The ICL lab has over 15 years of experience developing novel therapy for regenerative medicine being the first to publish work on transforming adult hematopoietic CD34+ cells into functioning insulin secreting surrogates using small activating RNA duplexes. This was considered a disruptive technology for regenerative medicine as this avoided insertional gene editing approaches for targeted gene upregulation. Prof Nagy Habib and Dr Vikash Reebye are the founding researchers of MiNA Therapeutics which develops CEBPA-saRNA. This therapeutic oligonucleotide formulated in NOV340, lipid nanoparticles is the first saRNA drug that has progressed to a Phase 2 clinical study. Over 140 cancer patients have been treated with this gene activating (saRNA) drug with an impressive safety profile. Prof Nagy Habib and Dr Vikash Reebye are hence perfectly suited to develop saRNA based drugs to target HRF (WP 5 and 6).
	The contribution of Erasmus Medical University Rotterdam (EMC) will be led by Drs Bart Haagmans and Martje Fentener van Vlissingen. Dr Haagmans is a principal investigator in the Virosciences department of EMC where his research has been focusing on the pathogenesis of emerging viral infections, including SARS, MERS and more recently COVID-19. Dr Haagmans’ contribution to corona virology has been major and includes, among others the characterization of the genome of MERS-CoV and identification of the reservoir species, the identification of the virus’ receptor, and extensive work on the pathogenesis of SARS and COVID-19. Dr Fentener van Vlissingen is a veterinarian by training and the Head of the Erasmus Centre for Animal Research; she will provide all the guidance for the implementation of the planned in vivo work in WP 6.

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