New antiviral agents With sugar against viruses
Vaccinations can protect against viral diseases. However, vaccines are only available against comparatively few viruses – as the current corona pandemic shows once again – which is why the development of antiviral agents is of enormous relevance. A team of researchers from Düsseldorf and Münster has now investigated the potential of long-chain sugar.
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(Image: University of Düsseldorf)
Düsseldorf – Viruses have been with people for a lifetime, they trigger a variety of diseases; the current corona pandemic is just one example. Vaccination provides effective protection against a viral disease, but vaccines are only available against a few viruses. Therefore, antiviral agents must be found that can prevent or fight a virus infection.
A successful strategy was to use special molecules to block viral proteins that would otherwise help the virus to dock onto the human cell. Once a virus has settled on the surface of the cell, it can inject its genetic material into the cell and convert it for its own purposes. However, many antivirals lose their effectiveness over time because viruses mutate very quickly and can adapt to the immune system so often.
A research team led by Professor Dr. Laura Hartmann from the Chair of Macromolecular Chemistry at Heinrich-Heine University Düsseldorf and the Münster Professor Dr. Mario Schelhaas from the Institute of Cellular Virology in collaboration with Prof. Dr. Nicole Snyder from Davidson College, North Carolina, USA, attempted to prevent the virus from first contacting the cell so that the infection chain could not start.
Artificial candy canes block viruses
Viruses often bind to sugar molecules on the cell surface with special proteins. These sugars include the long-chain, highly negatively charged glycosaminoglycans (GAG). They also include heparan sulfate. It has already been known that GAG can reduce viral infections when administered externally. However, natural sugar mixtures have side effects that are due to their own biological function in the body or to impurities.
The research team is now using the advantages of the GAG and at the same time eliminating its disadvantages. The idea: One uses artificial molecules, so-called glycomimetics, produced at HHU under controlled conditions. They consist of a long synthetic scaffold with small sugar molecules attached to the side arms. Both shorter chains with up to ten side sugars (so-called oligomers) and long chains with up to 80 sugars, the glycopolymers, were produced in Düsseldorf. In order to be as similar as possible to the GAGs, the chemists linked sulfate groups to the sugars.
Subsequently, Prof. Schelhaas at the University of Münster tested the antiviral properties of these “candy canes” of different lengths on cell cultures. First, his research group used them against human papilloma viruses, which can cause cervical cancer, among other things. It was shown that both the short and long chain synthetic molecules have an antiviral effect, but in two different ways. While the more effective, long-chain molecules hindered cell docking as expected, the short-chain molecules showed antiviral activity beyond docking, so they are likely to be active longer in the body.
Prof. Schelhaas: “Most likely, the long-chain molecules occupy the places on the virus by means of which it binds to the cell and thus block it. The short chain molecules cannot block these sites. In the following we want to examine the hypothesis whether these molecules hinder the rearrangement of proteins in the virus so that the viruses cannot infiltrate their genetic material into the cell. ”
Effective against various viruses
The efficacy was also confirmed for the papilloma viruses in an animal model. In addition, the active substances were active against four other viruses – including herpes viruses, which can cause lip sores and meningitis, and influenza viruses, which cause flu. Prof. Hartmann: “The glycomimetics are promising drug molecules that can potentially be used against a large number of different viruses. In a subsequent step, the exact mode of action of the glycomimetics is examined and how they can be further optimized. “
Prof. Schelhaas adds: “One subject of further research will be how quickly viruses can adapt to this new class of active ingredient. With short-chain molecules in particular, there is hope that the viruses will find it harder to find countermeasures. ”
The project was supported by the German Research Foundation as part of the funding of the Virocarb research group and by the Federal Ministry of Education and Research as part of the funding of the European Infect-ERA consortium HPV-MOTIVA. HHU’s Heine Research Academies (HeRA) also supported the exchange program with Prof. Snyder’s group.
Original publication: Laura Soria-Martinez, Sebastian Bauer, Markus Giesler, Sonja Schelhaas, Jennifer Materlik, Kevin Janus, Patrick Pierzyna, Miriam Becker, Nicole L. Snyder, Laura Hartmann and Mario Schelhaas, Prophylactic Antiviral Activity of Sulfated Glycomimetic Oligomers and Polymers, J. Am . Chem. Soc. 2020, 142, 11, 5252-5265; DOI: 10.1021 / jacs.9b13484
* Dr.rer.nat. A. Claussen: Heinrich Heine University Düsseldorf, 40225 Düsseldorf
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