CARE – Infographic – Work Package 5 – identifying immune markers contributing to the host immune responses to SARS-CoV-2 infection and their correlations with clinical and virological outcomes​

CARE has 8 Work Packages but do you know what each one does? Here, you can learn about the Work Package 5 team, their objectives, their partners, their breakthrough moments and more.

The infographic is also available here

CARE’s Young Researchers – Introducing Manon Laporte, PhD, KU Leuven

Read about how Manon’s work in phenotypic antiviral screening enabled the discovery of a novel target in the replication cycle of coronaviruses and a small molecule inhibitor that can address that target, plus how this approach may benefit future pandemic preparedness across many virus types.

CARE (Corona Accelerated R&D in Europe) is the largest European research initiative addressing the challenges of COVID-19. It comprises 38 partners, from both industry and academia, in a set-up of eight multidisciplinary work-packages (WPs). In this series, we highlight the work of some of the young researchers involved in CARE as part of their PhD or postdoctoral work. Here, we learn how this opportunity has benefited Manon, while simultaneously benefiting CARE and its ambition to help society defeat COVID-19 and future pandemics.

What experience did you have working on a Public Private Partnership before joining CARE? 

I had no experience working on a PPP before but many of my current colleagues did.

 

How did your involvement in CARE come about?

I joined the group of Johan Neyts (the academic lead of Work Package 1) two years ago, approximately one year after the start of CARE. At that point, I had two years’ experience working with SARS-CoV-2, both at the Rega Institute in Leuven with my former Principal Investigator, Lieve Naesens and during my postdoc at the Garcia-Sastre lab in New York at the Icahn School of Medicine at Mount Sinai. Given my experience with SARS-CoV-2, I started working on the CARE antiviral projects together with Dirk Jochmans, research manager of Johan Neyts’ group.

 

Tell us about the work you have been doing in the CARE consortium

I’m part of the team working on Work Package 1: “Anti-coronavirus drug discovery in phenotypic virus-cell-based assays.” I plan and oversee the in vitro antiviral testing for different partners within CARE. I also helped to establish antiviral assays for high throughput screening using our unique lab-in-a box system CAPS-IT (https://rega.kuleuven.be/cmt/capsit) and I have set up several mode-of-action assays to elucidate the working mechanism of newly identified hits.

Our biggest project within CARE is the coronavirus M assembly inhibitor project together with CD3 (https://www.cd3.be/) and CISTIM (https://www.cistim.be/). When I joined two years ago, we had two interesting compound series. I have been very closely involved in the optimization process and in solving the molecular mechanism of action of ‘series 8’. These compounds inhibit the virus via an entirely novel and hitherto unknown way, namely by blocking the viral membrane (M) protein, the key regulator of coronavirus assembly.

 

What highlights can you share from your time in the CARE consortium so far?

Scientifically I feel very fortunate to be able to work on the coronavirus assembly inhibitor story. We discovered a novel druggable target in the replication cycle of coronaviruses and a small molecule inhibitor that can address that target.

In science, you sometimes have to be a little lucky and it is an amazing opportunity to work on such an exciting story with a great group of people, both within our team at KU Leuven, the medicinal chemists at CD3 and CISTIM, and our collaborators at other institutes. Within CARE, especially with the team of Daniel Hurdiss (Utrecht University) and the team of Eric Snijder (Leiden University Medical Centre).

 

Why does this work matter?

We prove again that phenotypic antiviral screening is a successful way of identifying novel antiviral targets. Until today, effective antiviral therapies for many viruses with epidemic and pandemic potential are still lacking (e.g., paramyxo-, pneumo-, bunya-, flavi-, toga-, filo-, enteroviruses). The mission of our lab (www.antivirals.be) is to develop small-molecule antiviral drugs (or combinations thereof) against these viruses using phenotypic high-throughput screening as a starting point. Hits from these screening campaigns are further optimized and we try to unravel their mode of action which often leads to the discovery of novel antiviral targets, as was the case for the coronavirus M targeting compounds. Besides my work on SARS-CoV-2, I am currently focusing on a small molecule discovery project for henipaviruses. Nipah virus is a highly lethal paramyxovirus (case fatality rate is estimated at 40% to 75%) that causes almost yearly outbreaks and can be transmitted from human to human. There is no treatment or vaccine available and Nipah virus is on the WHO R&D blueprint list of priority diseases. It is our goal to discover novel small-molecule inhibitors with pan-henipa coverage so that, in the event of a big outbreak we don’t lag behind with antiviral therapy as was the case during the COVID-19 outbreak.

 

How have you benefited from your involvement in CARE?

I have benefited by expanding my network significantly. Thanks to CARE it is possible to work with other experts in the field in a very efficient way. The amount of data we can collect by working together is truly unique.

CARE – Infographic – Work Package 4 – Generation and characterisation of monoclonal antibodies against SARS-CoV-2 and related coronaviruses

CARE has 8 Work Packages but do you know what each one does? Here, you can learn about the Work Package 4 team, their objectives, their partners, their breakthrough moments and more.

The infographic is also available here

Introducing NUVISAN – a CARE Industry organisation

Founded in Europe in 1989 as an independent, family-owned contract research organization (CRO), NUVISAN was set up with a clear purpose: to leverage science to foster positive change and enhance the lives of patients. Initially providing bioanalytical laboratory services and PK/PD studies, the company later expanded to other areas, such as early discovery, safety testing, clinical trial management, and regulatory support. It has grown significantly since its founding and has expanded its services and capabilities to meet the changing needs of its clients.

Operating under the name NUVISAN since 2010, ALS Limited, the global leader in testing, acquired NUVISAN on April 1, 2024, forming the most advanced drug discovery and development organization and providing solutions across continents. NUVISAN is a fully integrated contract research and development and manufacturing organization (CRO/CDMO) that offers unique, high-quality, and tailored integrated solutions along the drug discovery and development value chain. These include:

  • Target Identification and Validation
  • Target-to-Lead
  • Lead-to-Candidate
  • Preclinical
  • Clinical

Why did NUVISAN choose to get involved in CARE?

NUVISAN chose to get involved in order to support the development of therapeutics in addressing the current or future coronavirus outbreaks. The CARE consortium offered the exciting opportunity for NUVISAN to team up with renowned research organisations jointly discovering and developing new treatment options to treat the current and future coronavirus outbreaks.

 

What has NUVISAN delivered for CARE?

In addition to our initiator role for the CARE project and bringing different expertise in medicinal chemistry (Work Package 3) and in vitro ADMET compound profiling (Work Package 6) into the team, NUVISAN is a project lead for a joint Hit-2-Lead project together with Servier (high throughput screening), Merck and Takeda (synthesis) and Iktos (AI, design), KU Leuven and LUMC (antiviral assays), Université d’Aix-Marseille (biochemical & biophysical assays), Helmholtz-Zentrum Für Infektionsforschung Gmbh and The Institute of Virology and Immunology (in vivo compound profiling).

These collaborative efforts have now achieved an in vivo proof-of-concept and the project is moved into lead optimization phase.

For more information about the different work packages, please click here

What benefits has NUVISAN enjoyed through participating in CARE?

Nico Brӓuer, NUVISAN PI for CARE comments: “We are delighted to be engaging with so many globally renowned research institutions and pharmaceutical companies in this impactful and exciting project. While collaborating on this joint endeavour, we continue to discover new ideas and unlock scientific innovation through extensive knowledge exchange and discussions with other members. Together, we can accelerate the development and utilization of effective therapies for patients around the world.”

 

In addition to Nico, the NUVISAN team includes

Want to know more about NUVISAN? click here.

CARE – Infographic – Work Package 3 Antiviral Drug Development: Hits to Leads.

CARE has 8 Work Packages but do you know what each one does? Here, you can learn about the Work Package 3 team, their objectives, their partners, their breakthrough moments and more.

The infographic is also available here

Published in PLoS Pathogens: picornaviruses modulate nucleotide metabolism

17 October 2024
Published in PLoS Pathogens: picornaviruses modulate nucleotide metabolism The CARE partner Utrecht University (UU) assessed the modulation of host metabolism by two picornaviruses using steady state as well as 13C-glucose tracing metabolomics. The family Picornaviridae, a large family of small, non-enveloped viruses with a single stranded positive sense RNA genome, includes many well-known human and [...]