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Academia-Industry Research and Development Opportunities for Picornaviruses

Final Report Summary - AIROPICO (Academia-Industry Research and Development Opportunities for Picornaviruses)

The AIROPico project aimed to investigate the following questions:
• How do picornaviruses cause disease?
• Can we develop a rapid diagnostic test for the detection of human picornaviruses to identify specific picornaviruses in patient material?
• Can we develop therapies against picornavirus infections?

The picornavirus family is a very large virus family and picornaviruses are the most commonly encountered infection agents in mankind. The most famous picornavirus—poliovirus—has been a terrible burden for mankind for centuries, and historically picornavirus research was thus predominantly focused on this virus. Polio has now been brought close to complete eradication, but multiple other picornaviruses, for example, rhinoviruses and enteroviruses, routinely infect humans. They cause a plethora of diseases ranging from mild respiratory infections to life-threatening encephalitis and acute flaccid paralysis.

Several large picornavirus epidemics and multiple smaller outbreaks have occurred recently, but we have no vaccines or antivirals to control them. The development of picornavirus therapies is hampered by our lack of understanding the virus biology. The AIROPico research project focuses on clinically relevant picornaviruses aiming to gain a deeper understanding of picornavirus biology and translate it into improving diagnostics and development of vaccines and antivirals.

AIROPico is the first EU consortium focusing solely on human picornavirus research. It is an Industry Academia Partnerships and Pathways (IAPP) project, and research is performed by researchers that are exchanged by their current employer to one of the other AIROPico partners.

AIROPico organized 8 very successful meetings/workshops uniting academia and industry. The major outcomes are highlighted below per workpackage:
1) Coxsackievirus B3 (CVB3) and CVB4 were produced with high quantity and purity. Structural studies identified the binding site in CVB3, the mode of drug action, and prediction of its effect on strain variants. The structure of CVB4 was solved.
2) Linear and conformational epitopes of several monoclonal antibodies and synthetic antibodies that recognise and/or neutralize human parechovirus were defined functionally and structurally.
3) Several potential mimitopes were identified on (non-)structural proteins of human parechoviruses 1 and 3 using the MVA technology (PB).
4) Standardized models were set up for virus-host interactions using human organoid cultures, enabling the culturing in human airway epithelial cells and human gut organoids.
5) A method for the rapid generation of PCR clones of viral sequences was developed. Infectious virus variants can be generated within one month, improving on the current methods available.
• One positive monoclonal cell line was rescued from HPeV-1-VP0 immunized animals.
• local projects to generate synthetic antibodies (Ab) to human parechoviruses and rhinoviral 3C protein and rescued pools of HPeV-VP0 and RV-3C protein-specific Abs.
• A mono-specific enterished, the researcher returns to the sending institute to disseminate the learned techniques, resulting in an optimal exchange of knowledge. oviral Ab was tested in mariPOC against cell-cultivated enteroviruses.
• A picornavirus-specific RT-qPCR kit was developed and validated as well as a low cost workflow for entero- and rhinoviral typing using RT-qPCR
• The “PrimariPOC study”, aims for clinical evaluation of mariPOC at AMC including interviews of GPs and customers.
• The chip for typing of rhinoviurses developed in the first period was clinically validated and introduced into a diagnostic setting
• A new enterovirus entry inhibitor (“Compound 17”) was characterized with a unique antiviral profile, which was key to investigating its binding mode using structural biology methods.

Seven excellent postdocs were recruited (for 6 positions). 1 each from UK, France, US and India, 2 back from US, 1 back from NL. 4 stayed in academic research, 1 stayed in a company position and 1 switched from academia to a company. 30 exchanges by 22 fellows (14 female and 8 male) have been implemented (6 ESRs, 4 technicians, 8 postdocs and 4 senior/staff persons). With a final output of AIROPico of > 20 scientific papers, Lay press interviews and the Chipron RV chip, AIROPico really made a significant contribution to Picornavirus Research and Development and resulted in many fruitful collaborations:

ArcDia-AMC >> MariPOC
UH-AMC >> structure, Abs HPeV3
UH-UTU >> structure, panAbs HPeV
UH-AMC >> structure, nAbs HPeV1
UH-AMC-PB >> HPeV biomarkers
REGA-UH>> antivirals, structure CVB3, CVB4
AMC-REGA>> 3D culture models, antiviral
AMC-TIB >> Chipron RV chip
UTU-TIB-AMC >> rapid testing and typing

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