No entry: Blocking viruses from entering cells

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.