MuTaLig: A multi-target paradigm for innovative drug discoveries

Everyone at some point in their life may need to take medication to treat an illness or disease. By finding new and better ways to create drugs, the COST Action Multi-target paradigm for innovative ligand identification in the drug discovery process (MuTaLig) helped improve the effectiveness and safety of the medications, which can ultimately benefit people's health and well-being.

Inspired by the Paul Ehrlich Euro-PhD network, and launched successfully in 2015, MuTaLig has focused on innovative drug discovery. Researchers embraced the 'multi-target paradigm', developing drugs that can interact with multiple protein targets using a single compound. This strategy enhances drug effectiveness, minimizes resistance, and reduces side effects. Consequently, these compounds can better combat complex diseases like cancer, Alzheimer's, and diabetes, leading to improved health outcomes and quality of life for patients

Professor Stefano Alcaro from Università Magna Graecia di Catanzaro (UMG) and the Chair of the Action MuTaLig shares with us the insights of this 'multi-target paradigm' which became particularly relevant during the pandemic. "Because the 'drug repurposing' or 'drug repositioning' is a method for revaluating old drugs or natural agents for other cures", says Stefano.

Overcoming challenges: engaging private institutions in MuTaLig

MuTaLig encountered a significant challenge in engaging private institutions, especially pharmaceutical or biotech companies. These companies value innovation but are cautious about sharing their exclusive chemical compounds, even with confidentiality agreements. Nevertheless, according to Stefano Alcaro, MuTaLig successfully used the COST Action networking tools, specifically Training Schools and STSMs to overcome this problem.

From the beginning of MuTaLig, two companies, Molecular Discovery Ltd (United Kingdom) and InteLigand Software Entwicklungs und Consulting (Austria), actively participated. InteLigand organized the first Action Training School in Vienna during 2017, introducing the Chemotheca tool. This tool was developed by a new spinoff enterprise called Net4Science, a direct outcome of the Action's efforts. Net4Science is an academic spinoff that offers services to pharma/biotech and agrifood/nutraceutical companies interested to speed up the drug discovery process or to clarify the mechanism of action of their bioactive compounds.

In addition, Net4Science participated in the organisation of some MuTaLig events and helped the Action to complete its dissemination activities.

MuTaLig: fostering collaboration and innovation in Multi-Targeting research

Before the start of the Action, the concept of 'multi-targeting' was known, but some aspects related to the revaluation of old or natural drugs remained unexplored. MuTaLig took on the challenge of building a strong scientific community focused on this topic, using a modern "virtual sharing opportunity" model implemented through Chemotheca, specially developed for this COST Action.

Initially aiming to implement 10,000 chemical entities, the MuTaLig MoU far surpassed expectations, incorporating over 64,000 chemical entities by the end of the Action. Remarkably, the development of Chemotheca was achieved without any direct funding from the COST Action, and it served as the foundation for several other initiatives involving participants from the MuTaLig community. The establishment of Net4Science was one of them. Furthermore, the success of MuTaLig extended to national-level grant proposals like PRIN and FISR during the pandemic, and locally like PSR.

These proposals are respectively focusing on the identification of multi-targeting agents against cancer, viral infections and olive flies.

Drug repurposing' or 'drug repositioning' is a method for revaluating old drugs or natural agents for other cures."

Prof. Stefano Alcaro, Chair of MuTaLig

Additionally, MuTaLig made a significant impact by using Chemotheca in training PhD students through applied research projects in collaboration with industrial European institutions. The Università Magna Graecia di Catanzaro (UMG) undertook two Life Science PhD projects in conjunction with Dompè Pharma Company in L'Aquila, Italy. The objective of these projects was to conduct a repurposing study on multi-targeting anti-tumor agents. A highlight of MuTaLig's accomplishments was the joint meeting held in June 2019 in Catanzaro, which brought together 150 participants from 20 different countries, including the Paul Ehrlich Euro-PhD network.

This stimulating environment led to the initiation of numerous new ideas and collaborations. MuTaLig also successfully organised a similar virtual event during the pandemic: the Paul Ehrlich Virtual Meeting in July 2021. The Action network has experienced remarkable growth, increasing the Paul Ehrlich Euro-PhD network from approximately 25 parties to 60 over the four years of the COST Action period.

Additionally, MuTaLig played a crucial role in the preparation of two special issues in Frontiers in Chemistry and European Journal of Medicinal Chemistry. These issues featured contributions from various research teams, all addressing topics central to MuTaLig.

MuTaLig against COVID-19

One notable success of MuTaLig was its initiative to establish connections with other COST Actions during the pandemic emergency in early 2020. The active involvement of MuTaLig led to the formation of an interdisciplinary network known as 'COST Actions against COVID-19'. In 2021, a prestigious scientific journal accepted a position paper co-authored by MuTaLig and eight other COST Actions. This publication highlights MuTaLig's collaboration with other COST Actions and provides valuable insights into the scientific community's cooperative efforts in combating SARS-CoV-2. Even today, the network continues to thrive and collaborate actively, establishing new contacts and further enhancing the network's reach and impact.