Assembly of coronavirus particles as a new target for the development of potent antiviral drugs
In a new Nature publication, we uncover a new strategy to combat coronavirus infections. Together with our collaborators we discovered coronavirus inhibitors that prevent the assembly of new viral particles.
SARS-CoV-2, the notorious coronavirus, held the world it its grip for a long time and continues to affect people today. Fortunately, in addition to vaccines, two different antiviral drugs for coronaviruses have been developed. These are primarily used for high-risk patients. Unfortunately, they are not perfect. One of the drugs must be administered directly into the bloodstream, meaning patients can only be treated in a hospital setting. Another coronavirus drug can be taken orally but interferes with the dosage of many other medications. ‘That is a complicating factor,’ explains Johan Neyts, Professor of Virology at KU Leuven. ‘There is a need for new SARS-CoV-2 drugs that can be taken as a simple pill and do not interfere with other medications. Additionally, we need new coronavirus inhibitors to prepare for the potential emergence of future dangerous coronaviruses.’
Attacks on all fronts
It is crucial to continue exploring new ways to combat coronaviruses. Together with the virology team led by Professor Johan Neyts, we tested over 350,000 molecules for activity against the SARS-CoV-2 coronavirus. The goal was to identify new molecules that inhibit the virus and could serve as a starting point for the development of a new drug. One of these hundreds of thousands of molecules was found to completely inhibit the production of new coronaviruses.
Once we had a lead compound, our teams worked to optimise it into a highly effective antiviral drug. This led to CIM-834, and we continue to make modifications to enhance its potency as an antiviral agent.
Together with our international partners, we investigated the precise mechanism behind CIM-834. The results show that CIM-834 completely hampers the assembly process of new viral particles. While the individual components of the virus are still produced, they are no longer successfully assembled into a new viral particle. This discovery has uncovered a new vulnerability in the coronavirus replication cycle. Furthermore, when administered orally, CIM-834 proved to be highly effective in animal models.
Although the corona crisis may seem like a thing of the past, the virus can still make people seriously ill. It is therefore crucial to ensure that the most vulnerable patients can be treated with antiviral drugs when they contract SARS-CoV-2. This underscores the importance of continuing to develop new drugs against the virus. Preparedness is also essential to be able to counter potential dangerous coronaviruses in the future. By developing new potent antiviral drugs and uncovering a new weak spot in the virus’s replication cycle, we have taken an important step forward in the fight against coronaviruses—not only against SARS-CoV-2 but also against potential future coronaviruses.
More information
The paper ‘An orally efficacious coronavirus assembly inhibitor that targets the viral M protein’ by Laporte et al. was published in Nature (DOI: 10.1038/s41586-025-08773-x).
This research was a collaboration between KU Leuven, CD3, CISTIM Leuven vzw, and research teams from the Netherlands (Utrecht University and Leiden University), Germany (Heidelberg University and Lübeck University), France (University of Lille and Aix-Marseille University), Japan (University of Tokyo and Kyoto University), and Poland (Jagiellonian University in Krakow). It was funded by the Innovative Medicines Initiative 2 Joint Undertaking (JU) CARE Project under grant agreement No 101005077 (www.imi-care.eu/), EU Horizon 2020 SCORE, PANVIPREP, DURABLE, the Bill & Melinda Gates Foundation, the COVID-19 Fund of KU Leuven/UZ Leuven, and the Research Foundation – Flanders (FWO).
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