The COVID-19 pandemic has highlighted the importance of effective drugs to combat infectious diseases and has led to numerous innovations and developments in antiviral agents. At the same time, however, it may also have provided a significant boost to the spread of antibiotic resistance. This is because many of the patients infected with SARS-CoV-2 were treated with antibiotics as a precautionary measure to prevent additional bacterial infection - and the more frequently antibiotics are used, the greater the likelihood that resistance will develop. To counteract this trend, innovative antibiotics with previously unused mechanisms of action are urgently needed. Prof Anna Hirsch has set herself the task of developing precisely such active substances. Hirsch is head of the Department of Drug Design and Optimization at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), professor of medicinal chemistry at Saarland University and scientist in the research area "Novel Antibiotics" at the German Center for Infection Research (DZIF). HIPS is a site of the Helmholtz Centre for Infection Research (HZI) in collaboration with Saarland University.
As part of her 2018 ERC Starting Grant, Anna Hirsch has already succeeded in identifying a number of novel molecules that target previously unused structures in bacteria and thus represent a promising starting point for the development of resistance-breaking antibiotics. One of these target structures is a protein called DnaN. This protein is an essential part of the bacterial machinery responsible for repairing and producing new DNA. Thus, if the activity of DnaN is impaired, the affected bacteria can no longer reproduce. This makes DnaN an extremely attractive target for the development of new active substances. The ERC Proof of Concept funding now obtained will give Anna Hirsch the opportunity to further optimize her most promising drug candidate.
"The goal is to improve our current best molecule to the point where we can nominate a preclinical candidate at the end of the project. For this, we rely on the already established structure-activity relationships and binding mode of our DnaN inhibitor. This is a very important step towards a potential application. Once this candidate is found, we can start testing and optimizing our compound for human application," says Hirsch. "Along the way, we are getting additional support from partners and mentors in the pharmaceutical industry. Such knowledge is invaluable in order to eventually come up with a product that can contribute to everyday clinical practice in a meaningful way." In addition to researchers from Anna Hirsch's department, scientists at HIPS, HZI and the Research Center Borstel have also been involved in the project.
The managing director of HIPS, Prof Rolf Müller, is also enthusiastic about the renewed ERC funding: "A major problem in antibiotics research is that only insufficient funding is provided for the transition from basic research to application. We are all the more pleased that Anna Hirsch has now succeeded in acquiring such funding. Only a few scientists succeed in obtaining funding from one of the prestigious ERC programs during the course of their careers. The fact that Anna Hirsch has now achieved this for the second time makes us proud and shows that she is one of the top researchers in her field."
The funding obtained by Hirsch comprises €150,000 and has a duration of 12 months. The project is expected to start in the second quarter of 2023.
