September 5th 2024

CARE’s Young Researcher – Manon Laporte

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.