Researchers design broad-spectrum antiviral agents to stop viruses entering cells

To achieve this, the two researchers intend to block a step that occurs at the very start of the viral infection process: the binding of viruses to sugar molecules on the cell surface. The Volkswagen Foundation is now supporting the development of such inhibitors with funding of almost one million euros.

Many viruses use the cell's own sugar molecules to bind to the cell surface and initiate infection. As this step is common among a range of different viruses, it can be exploited to develop broad-spectrum antiviral agents. The project led by chemist Alexander Titz and biologist Christian Sieben aims to establish an innovative platform for developing viral entry inhibitors, focusing particularly on respiratory viruses and other viruses that pose a pandemic risk. These include influenza A viruses, SARS-CoV-2, and other zoonotic pathogens that can cross from animals to humans.

The researchers and their teams are pursuing an innovative strategy: they are designing molecules, known as sialomimetics, which mimic the natural sugar structures found on the surface of human cells. This sugar coat, also known as the glycocalyx, plays a crucial role in infection by many viruses. Sialic acids on the cell surface serve as docking points that influenza viruses and coronaviruses use to initiate infection. The researchers aim to disrupt this binding process by developing molecules that attach to viral proteins more effectively than natural sugar chains. This will stop the viral binding proteins from attaching to the cell surface, thus preventing infection. During the initial funding period from the Volkswagen Foundation, the researchers have already identified promising drug candidates, which they now intend to optimize further.

A key to protection against many viruses

'Specific drugs are currently available for only a small number of viruses. There is no equivalent of broad-spectrum antibiotics for viral infections,' says Professor Alexander Titz, who also leads a research group at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), a research institute of HZI run in cooperation with Saarland University, and is a scientist at the German Center for Infection Research (DZIF). 'We aim to block the very first step of infection and want to do this for many different viruses at the same time. That is the key to establishing broadly effective therapies.'

'Thanks to renewed funding from the Volkswagen Foundation, we can take an important step forward in the development of new antiviral compounds while also expanding our understanding of the how viruses interact with human cells,' says Professor Christian Sieben, head of the junior research group Nano Infection Biology at HZI. 'Our goal is to create a drug-development platform that can be used not only against influenza viruses and coronaviruses, but also in future pandemics caused by as-yet-unknown viruses.'

Press release by the Volkswagen Foundation on the funding initiative ‘Innovative Approaches to Antiviral Drug Development’.

For further enquiries, please contact:
Professor Dr Alexander Titz
Organic and Pharmaceutical Chemistry, Saarland University
https://www.uni-saarland.de/fakultaet/nt/profs-gruppen/professuren/chemie/prof-dr-alexander-titz.html