Results Announced for the EUTOPIA_HEALTH Seed Funding Call

Pannexin 1 channels facilitate paracrine communication and play a crucial role in inflammatory responses. Inhibiting these channels represents a promising strategy for treating inflammatory disorders. Recent studies from Partner 2 (Raf Van Campenhout-Vrije Universiteit Brussel) have demonstrated that blocking pannexin 1 channels effectively reduces inflammation. Building on these findings, this project aims to identify and optimise novel small-molecule pannexin 1 channel inhibitors with improved specificity, selectivity, affinity and efficacy as potential anti-inflammatory drugs.

To achieve this goal, a highly interdisciplinary collaboration will be established between the Cluster Lead (Tihomir Tomašič, University of Ljubljana), Partner 1 (Chiara Zanato, CY Cergy Paris University) and Raf Van Campenhout. The group of Tihomir Tomašič will play a central role in hit identification by high-throughput virtual screening and hit optimisation, ensuring the rational design of potent pannexin 1 channel inhibitors. The group of Chiara Zanato will contribute complementary expertise in synthetic organic chemistry, developing the synthesis of the most promising hit compounds and their analogues aimed at improving their properties during hit expansion and hit-to-lead optimisation. Promising compounds will be subjected to in vitro functional analysis by the group of Raf Van Campenhout to evaluate their interaction with pannexin 1 proteins and their ability to block pannexin 1 channel activity. The most effective inhibitors will then be further optimised and validated for their potential to mitigate inflammation in vitro.

This highly interdisciplinary project integrates computational chemistry, medicinal chemistry and experimental biology, fostering knowledge exchange among partners and strengthening Europe’s research network. The Cluster Lead will play a pivotal role in advancing pannexin 1-targeting drug development, positioning the consortium at the forefront of innovative treatments for hard-to-treat inflammatory conditions.

Antimicrobial resistance is one of the greatest threats to global health, particularly due to the rise of multidrug-resistant Gram-negative bacteria. Traditional antibiotics are becoming less effective, and new treatment options are urgently needed. This project aims to develop new antibacterial compounds that target two essential bacterial enzymes, penicillin-binding protein (PBP) 2 and PBP3, which play critical roles in bacterial cell wall synthesis and survival.

The overall aim of DUALACTAM is to develop novel monocyclic β-lactam antibiotics capable of simultaneously inhibiting penicillin-binding proteins PBP2 and PBP3, two essential enzymes involved in bacterial cell elongation and division. To achieve this goal, a highly interdisciplinary collaboration has been established between the Cluster Lead, Prof. Dr. Stanislav Gobec (University of Ljubljana, Slovenia), Prof. Dr. David Roper (University of Warwick, United Kingdom), and Prof. Dr. Csaba Paizs (Babeș-Bolyai University, Romania).

The research group of Prof. Dr. Stanislav Gobec is responsible for computational drug design, medicinal chemistry, synthesis of novel monocyclic β-lactams, and optimisation of the most promising compounds. The group of Prof. Dr. David Roper contributes expertise in bacterial cell wall biology, protein expression and purification, biochemical and microbiological evaluation, as well as structural studies of inhibitor binding. The group of Prof. Dr. Csaba Paizs provides expertise in biocatalysis, enzyme engineering, and stereoselective synthesis, supporting the preparation and optimisation of novel β-lactam derivatives. Together, the partners aim to identify and validate new lead compounds with the potential to address antimicrobial resistance.

The project will contribute to the global effort to combat antimicrobial resistance by advancing innovative solutions to a critical health challenge.