In January 2021, a nationwide research project will start that aims to develop a targeted therapy against SARS-CoV-2. It is funded by the German Federal Ministry of Education and Research (BMBF) as part of the InfectControl consortium with circa 2.3 million euros. The participating institutions from Jena, Würzburg and Hamburg are pursuing a promising approach with which the virus can be eliminated by the immune system in a targeted manner.

We would all like to see an end to the pandemic as quickly as possible. Therefore, in addition to preventive measures such as vaccination campaigns and contact reduction, it is equally important to develop effective therapies and drugs against SARS-CoV-2 as quickly as possible. To date, there are only a few promising therapeutic approaches.

Joining forces

Researchers from the Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute - (Leibniz-HKI), Friedrich Schiller University Jena, Julius Maximilian University Würzburg and the Heinrich Pette Institute, Leibniz Institute for Experimental Virology in Hamburg are combining their expertise in drug development, infectious medicine and virology to jointly contribute to the management of the COVID-19 pandemic.

The goal of the project is to develop a novel therapeutic approach for SARS-CoV-2 infections. It is also hoped that the knowledge gained will help to rapidly develop new therapeutics in the event of potential future pathogen outbreaks.

Supporting the immune system

The scientists want to enable the human immune system to recognize the virus particles and eliminate them in a targeted manner: In doing so, they are taking advantage of the highly specific interaction between the virus and the human cells: According to the lock-and-key principle, a surface protein - the so-called spike protein - of the SARS coronavirus-2 interacts with receptors of human cells. Due to its small size and because it is absorbed into the cell interior, human immune cells, the so-called phagocytes, cannot take up the virus and destroy it.

Axel Brakhage is spokesman for InfectControl and director of Leibniz-HKI. "We are developing customized aggregates that mimic the receptor of the human cell. Our hope is that the viruses will eventually bind to the artificial receptor and not to the human cell. This would allow the cells of the immune system to recognize the viruses and eliminate them on their own," says the molecular biologist, who also holds a chair at the University of Jena.

Chemist Florian Kloß adds, "We will analyze the potential new active substances for functionality and compatibility through laboratory tests and examine possibilities for therapeutic use." He heads the Antiinfectives Transfer Group at Leibniz-HKI and, together with his team, is dedicated to the preclinical and early clinical development of promising compounds.

"The basis of the tailor-made aggregates are synthetic macromolecules that are decorated with the receptor units. These macromolecules are subsequently formulated into nanoparticles. With the receptor units on the surface, the particles are ready to bind the viruses to them," explains Ulrich S. Schubert, chemist and materials scientist at Friedrich Schiller University Jena. He is the spokesperson for the DFG's "PolyTarget" collaborative research centre, which focuses on new pharmaceutical polymers and innovative nanoparticles for personalised nanomedicine.

Würzburg virologist Simone Backes and immunologist Georg Gasteiger, head of the Max Planck Research Group for Systems Immunology at the Julius Maximilians University of Würzburg, will then investigate whether the agents developed at the Leibniz-HKI can prevent coronavirus infection: They want to discover whether the artificial aggregates actually mark the coronaviruses and make them visible for attack by the human immune system.

"In the project, we will additionally evaluate the antiviral properties of the new agents against SARS-CoV-2 in a human lung model," adds Gülsah Gabriel. She heads the department "Viral Zoonoses-One Health" at the Heinrich Pette Institute, Leibniz Institute for Experimental Virology in Hamburg. Together with her team, she investigates the molecular mechanisms of virus transmission between different species as well as the pathogenesis of zoonotic viruses.

InfectControl - together strong against infections

The InfectControl research network brings together partners from industry, science and society to jointly develop new strategies to combat infectious diseases.