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12/04/2021

11/12/2021

On the leap to new antiviral agents

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The Federal Agency for Disruptive Innovation (SPRIND) has announced the participants of the first SPRIND Challenge "A Quantum Leap for New Antiviral Agents". From 45 applications from Germany and Europe, the jury selected a total of nine teams. Prof Mark Brönstrup from the Helmholtz Centre for Infection Research (HZI) in Braunschweig and Prof Chase Beisel from the Helmholtz Institute for RNA-based Infection Research (HIRI), a joint institution of the HZI with the Julius-Maximilians-Universität Würzburg (JMU), convinced the jury with the projects they led.

The HZI scientists Prof Carlos A. Guzmán and Dr Christian Sieben are involved in two other projects as cooperation partners. The teams will each receive up to 700,000 euros in the first year of the three-year competition to develop new drug candidates against viral diseases.

The Covid-19 pandemic, along with many previous epidemics, has clearly shown that viruses are a threat to human health worldwide. Despite the considerable success of vaccines, antiviral drugs are also needed to help those who are ill. For many viral diseases that have been with us for a long time, there are still no effective drugs.

The outbreaks of SARS-CoV-1, MERS-CoV, Ebola or influenza make it clear that we must prepare for future epidemics and pandemics. In order to achieve a breakthrough in the development of new antiviral drugs, the Federal Agency for Disruptive Innovation has called for this SPRIND Challenge. The jury from science and industry selected four teams with HZI participation.

Prof Mark Brönstrup, head of the department "Chemical Biology", and his team PROTAC are focusing on the degradation of viral components by the host cell. To this end, PROTAC is developing artificial molecules that bind both viral proteins and cellular quality control proteins, thereby bringing them into spatial proximity. "Our core idea is that you don't just temporarily block viral proteins, you degrade them through the body's cells. The technique has a platform character and can be quickly adapted to newly emerging viruses," says Brönstrup.

"To this end, we have assembled a team from academic research and industry that covers all the necessary competences." In addition to Brönstrup, the PROTAC team consists of experts in coronaviruses and drug design (Rolf Hilgenfeld, University of Lübeck), modelling (Katharina Rox, PK/PD Unit at HZI), pharmacology (Marjolein Kikkert, Leiden University/Netherlands) and drug synthesis and testing (Hanna Maple and Graham Marsh, BioTechne/England).

Bacteria have developed numerous defence systems to defend themselves against viruses that infect bacteria. The CRISPR-Cas gene scissors, which are also based on the bacterial immune system, are the research focus of Prof Chase Beisel's research group "Synthetic RNA Biology" at HIRI. With his team BacDefense, Beisel wants to take advantage of the diversity of bacterial defences as a possible new source of antiviral agents. The researchers are looking for a defence system that is also active against viral infections in human cells and can be effectively transported into the cells.

Dr Mathias Munschauer, also from HIRI, and Prof Claus-Michael Lehr from the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), a site of the HZI in cooperation with Saarland University, are contributing their expertise on viral infections and drug transport to the team. In addition to the HZI researchers, scientists from the University of Heidelberg and LMU Munich are also involved in the project.

Dr Christian Sieben, head of the junior research group "Nanoinfection Biology", is a member of the "MucBoost" team, which also receives funding and is coordinated by Dr Daniel Lauster at Freie Universität Berlin. The aim of the project is to strengthen the natural mucous membrane barrier in the respiratory tract. The researchers want to equip the mucus produced there with molecules that specifically bind viruses. This supports the removal of viruses before they can adhere to a suitable host cell and trigger an infection.

The HZI project quartet is completed by Prof Carlos A. Guzmán, head of the department "Vaccinology and Applied Microbiology", with the consortium "EXIGENT", coordinated by Dr Barbara Ensoli from the Italian Istituto Superiore di Sanità (ISS). EXIGENT will develop up to phase 1 clinical trials molecules with a dual antiviral activity by simultaneously blocking viruses and promoting immune defence mechanisms against a broad spectrum of viral infections.

"We are very pleased that the HZI was so strongly represented in this competition of ideas and performed excellently," says Prof Dirk Heinz, Scientific Director of the HZI. "This success shows that our scientists are pursuing highly innovative approaches to combat viral diseases even more effectively in the future."

About SPRIND

The Federal Agency for Disruptive Innovation (SPRIND) is a subsidiary of the German government and was founded in December 2019. Its mission is to identify, develop and finance groundbreaking civil innovations. Its innovation competitions, so-called SPRIND Challenges, aim to result in solutions for the major societal and technological challenges of our time.

» More about SPRIND Challenge

Source: Helmholtz Centre for Infection Research