Europe’s largest initiative launches to accelerate therapy development for COVID-19 and future coronavirus threats

The CARE consortium is the largest undertaking of its kind dedicated to discovering and developing urgently needed treatment options for COVID-19. The initiative is committed to a long-term understanding of the disease and development of therapies for COVID-19 and future coronavirus threats in addition to urgent efforts to repurpose existing therapies as potential immediate response. The CARE consortium brings together the leading expertise and projects of 37 teams, including the virology group of Utrecht University.

With a grant totaling € 77.7 million, the new CARE consortium will accelerate the discovery and development of urgently needed medicines to treat SARS-CoV-2, the virus that causes COVID-19. Prof. Frank van Kuppeveld, head of the Virology group of Utrecht University: ‘The CARE consortium is a unique opportunity to translate our long-standing experience in coronavirus research in important therapeutic applications to treat COVID-19 patients and to prepare against future pandemics caused by newly emerging coronaviruses.’ 

Development of antiviral compounds and antibodies

Uniting some of the most innovative and experienced scientists from all relevant areas CARE will maximize synergies and complementarities with other initiatives, to accelerate the path to providing solutions for the current COVID-19 pandemic as well as future coronavirus outbreaks. Van Kuppeveld: ‘We will contribute our expertise in coronavirus research to the identification and development of (broad-protective) antiviral compounds and protective antibodies against SARS-CoV-2 and other coronaviruses.’ After testing in the laboratory, the project will advance the most promising drug candidates to clinical trials in humans. 

Comprehensive short- and long-term response to COVID-19

CARE aims to create effective therapies with a positive safety profile for the COVID-19 pandemic (drug repositioning), and develop new drugs and antibodies specially designed to tackle the SARS-CoV-2 virus.  
The consortium builds on three pillars:

  • Drug repositioning, by screening and profiling compound libraries contributed by partners with the aim of rapidly progressing molecules to advanced stages of clinical testing.
  • Small-molecule drug discovery based on in silico screening and profiling of candidate compounds directed against SARS-CoV-2 and future coronavirus targets.
  • Virus neutralizing antibody discovery using fully human phage and yeast display, immunisation of humanised animal models, patient B cells and in silico design.

Closely integrated with these pillars are work streams focusing on the refinement of candidate compounds through a comprehensive medicinal chemistry campaign, systems biology research and pre-clinical and clinical evaluation of molecules from all three pillars. The systems biology work package will investigate the viral pathophysiology to increase our understanding of the interplay between virus infection stages and human immune responses. It will identify disease markers, to inform therapy development and improve clinical trial design and monitoring of Phase 1 and 2 trials investigating new therapeutics developed by CARE. 

Prof. Alexandre Bonvin is leading the virtual drug screening task in CARE. In that context, using their HADDOCK software, the Computational Structural Biology group has already performed a drug repurposing screen of over 2000 approved drugs against three main targets: the SARS-CoV-2 main protease and RNA-dependent RNA polymerase, and the human ACE2 receptor. A number of interesting candidates are currently being tested in collaboration with Prof. Van Kuppeveld.

Acknowledgement

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 101005077. The JU receives support from the European Union’s Horizon 2020 research and innovation programme, European Federation of Pharmaceutical Industries and Associations, Bill & Melinda Gates Foundation, Global Health Drug Discovery Institute, University Of Dundee.

Partners

CARE is a five year project bringing together 37 partners from Belgium, China, Denmark, France, Germany, the Netherlands, Poland, Spain, Switzerland, the UK and the US, and is led by VRI-Inserm (French National Institute of Health and Medical Research, Paris, France), Janssen Pharmaceutica NV (Beerse, Belgium), and Takeda Pharmaceuticals International AG, (Zurich, Switzerland). It integrates partners’ COVID-19 projects ongoing since February 2020.