Many viruses use cellular sugar molecules to bind to the cell surface and initiate infection. Since this step is common among various viruses, it can be exploited to develop broadly effective antiviral agents. The goal of the project led by chemist Alexander Titz and biologist Christian Sieben is to create an innovative platform for developing viral entry inhibitors—specifically targeting respiratory viruses and other viruses that pose a pandemic risk. These include, among others, influenza A viruses, SARS-CoV-2, and other zoonotic pathogens that can spill over from animals to humans.
The researchers and their teams are pursuing an innovative strategy: They are designing molecules, known as sialomimetics, that mimic the natural sugar structures on the surface of human cells. This sugar coat, also called the glycocalyx, is crucial for the infection of many viruses. In particular, sialic acids on the cell surface serve as anchor points for influenza and coronaviruses to initiate infection. The researchers aim to specifically disrupt this binding by developing molecules that attach more effectively to the viral proteins than the natural sugar chains. This is intended to block the viral binding proteins and thus prevent cell binding and infection. During the initial funding period from the Volkswagen Foundation, they have already identified promising drug candidates, which they now intend to further optimize.
“Specific drugs are currently available for only a few viruses. There is no such thing as a broad-spectrum antibiotic against viruses,” says Prof. Alexander Titz, who also leads a research group at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), a site of the HZI in cooperation with UdS, and is a scientist at the German Center for Infection Research (DZIF). “We block the very first step of infection and we do so for many different viruses at the same time. This is the key to broadly effective therapies.”
“Thanks to renewed funding from the Volkswagen Foundation, we can take an important step forward in the development of new antiviral agents and also expand our understanding of the interaction between viruses and human cells,” says Prof. Christian Sieben, head of the junior research group “Nano Infection Biology” at the HZI. “Our goal is to create a drug-development platform that can be used not only against influenza and coronaviruses but also for future pandemics caused by as-yet-unknown viruses.”
Helmholtz Institute for Pharmaceutical Research Saarland:
The Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) in Saarbrücken was founded jointly by the HZI and Saarland University in 2009. Scientists at HIPS develop and employ experimental and computational approaches to provide new active substances against infectious diseases, optimise them for use in humans and investigate how they can best be transported to their site of action in the human body. A special focus of the institute is on microbial natural products from soil bacteria and the human microbiota as well as innovative medicinal chemistry-driven approaches. https://www.helmholtz-hips.de/
Helmholtz Centre for Infection Research:
Scientists at the Helmholtz Centre for Infection Research (HZI) in Braunschweig and other locations in Germany study bacterial and viral infections and the body's defense mechanisms. They have in-depth expertise in natural product research and its use as a valuable source for novel anti-infectives. As a member of the Helmholtz Association and the German Center for Infection Research (DZIF), the HZI conducts translational research to lay the foundations for the development of novel therapies and vaccines against infectious diseases. https://www.helmholtz-hzi.de/en/