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
CARE’s Young Researchers – Introducing Holly Kerr, PhD, University of Edinburgh
Read about how Holly’s work in getting a better understanding of host response and resulting disease may help identify alternative or complementary approaches to direct-acting anti-virals by targeting the host.
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 Holly, 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 of being in a consortium of this type within a research context. However, before starting my PhD in 2020, I was recruited as a Laboratory Scientist at one of the UK’s Lighthouse Laboratories that were responsible for the mass COVID-19 testing effort. These labs were only possible due to a huge collaboration between industry, academia, and government. Working at the Lighthouse Lab gave me my first insight into the importance, impact and challenges of this kind of partnership.
Why did you decide to get involved in CARE?
My PhD project within the Tait-Burkard lab aims to better understand the host factors involved in SARS-CoV-2 and other human coronavirus infections. This includes following up the results of an RNAi Druggable Genome screen which was conducted as part of the CARE work package 5 research. Starting my PhD during the pandemic and following the work in the Lighthouse Lab, I was motivated to align my research project with the pandemic response. I was inspired by the cross-disciplinary and well-supported team effort that IMI CARE champions and feel grateful to have this consortium as a network within my research.
How did your involvement in CARE come about?
I was encouraged in the planning of my PhD project by my supervisor, Christine Tait-Burkard, to be involved in CARE, given my interest in host factors, antivirals and pandemic preparedness.
Tell us about the work you have been doing in the CARE consortium
My role in the CARE consortium involves analysing and validating an in vitro RNAi host factor screen of SARS-CoV-2 as part of the aims of Work Package 5. I have generated hit lists of genes involved in SARS-CoV-2 infection from the screen, compared these to host factors identified in other published work, including results within our work package, and conducted pathway and network analysis of our hits. I’ve validated two clusters of hits from anti-viral and pro-viral pathways and begun to decipher their role in infection. Identified host factors in our screen are “druggable”, in that drugs exist that target them, or are they are predicted to be targeted with drugs based on their structure. To follow up the results of our screen, I have been testing the use of repurposed host-directed anti-viral therapies in SARS-CoV-2 infection in vitro and I am planning to take forward promising candidates to an in vivo study this summer.
What highlights can you share from your time in the CARE consortium so far?
The highlight from my time in CARE has been attending the annual meeting in March this year in Leiden. It was exciting to see my work presented and helpful to receive feedback from a global group of experts. I really enjoyed meeting researchers from across the consortium, learning about the development of multiple promising treatment options from across the other work packages and being a part of the strategic discussions for the future of the consortium as we prepare for the next pandemic. As an early career researcher, these conversations are not often made accessible to me – I appreciated the opportunity to have the insight into decision making processes at this level.
Why does this work matter?
This work matters because despite the vast amount of research conducted following the emergence of the third highly pathogenic human coronavirus in the past 20 years, we are arguably still some way from being prepared for the next pandemic. In particular, we are yet to find effective, broad-spectrum, “off-the-shelf” therapeutic options. Coronaviruses continue to burden human, animal and environmental health and there is a risk of further emerging strains. By understanding the host response, we can better understand the resulting disease and perhaps identify alternative or complementary approaches to direct-acting antivirals by targeting the host.
What are or were the biggest challenges you have experienced (and how did you overcome them?)
Challenges I have experienced include keeping up with the variants of concern that evolved in real-time during our research. This was overcome though collaboration with clinical scientists and teamwork within the Tait-Burkard lab. We divided the labour to harness different skills from different scientists doing different tasks, including growing virus, testing stocks, sequencing, and then running relevant assays that tell us more about how the latest variants interact with the host within human cells.
How have you benefited from your involvement in CARE?
I have benefited by gaining insight into leading research in coronavirus biology, meeting experts from across Europe and putting my research in the context of other work under the same aim.
What advice would you give to someone getting involved in a Public Private Partnership?
I would tell them to do it, grab the opportunities that arise and try to enjoy the feeling of being the least experienced person in the room – it means you have the most to learn!
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:
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 Antiviral Research: A new fully automated dual-reporter HTS antiviral assay to facilitate drug discovery against SARS-CoV-2.
CARE partner KU Leuven developed a dual-reporter high-throughput screening (HTS) assay to facilitate antiviral drug discovery against SARS-CoV-2 using a fully automated, high-containment robot system.
For this purpose, by clonal selection, KU Leuven successfully obtained an A549 cell clone that expresses a strong fluorescent mCherry signal in the nucleus (for cytotoxicity evaluation) and that efficiently supports replication of a SARS-CoV-2 reporter virus that expresses the NeonGreen fluorescent reporter protein after infection (for antiviral potential), and this without being affected by virus-induced cytopathogenic effects. This dual-reporter system makes any staining steps redundant, and thus offers a convenient and robust strategy for phenotypic HTS. KU Leuven chose the A549 cell line, overexpressing the SARS-CoV-2 angiotensin converting enzyme 2 (ACE2) receptor and the spike priming protease transmembrane serine protease 2 (TMPRSS2) to develop this assay as this is a human airway epithelial cell line, a more relevant model than the Vero6 cell line, which is a monkey kidney-derived cell, often used for HTS campaigns against SARS-CoV-2.
Image acquisition and analysis processes were automated using the Caps-It research infrastructure, a fully automated robotic system enclosed in an isolator, which facilitates HTS on high biosafety organisms, as developed by KU Leuven. An in-house algorithm was created for cell counting, segmentation, and validation for calculation of the percentage of infected cells.
Two reference compounds with known antiviral activity against SARS-CoV-2, GS-441524 and PF-00835231, were tested in this assay and both resulted in antiviral activity against SARS-CoV-2 with similar EC50 and CC50 values reported in other publications, thus validating this novel assay.
This newly developed high-content imaging-based HTS assay, which is automated, scalable, and robust, is suitable for screening of large compound libraries.
To learn more, click here: Development of a robust and convenient dual-reporter high-throughput screening assay for SARS-CoV-2 antiviral drug discovery
