ASCRIBE: Screening of bioresources to identify new antiviral substances for the treatment of influenza infections

Influenza viruses of genera A and B usually cause uncomplicated febrile infections of the upper respiratory tract with respiratory symptoms in healthy individuals. In the case of severe courses, however, complications can occur, such as the development of primary influenza pneumonia or secondary bacterial infections, which can lead to the death of the patient. On average, about 1000 people die of influenza infection in Germany each year. In Germany, two drug classes are approved for the treatment of influenza: M2 ion channel blockers and neuraminidase inhibitors. However, the great genetic flexibility of the viruses means that there is a risk of rapid development of resistance. Because of the high prevalence of resistance in currently circulating influenza viruses, M2 ion channel blockers are no longer recommended for antiviral treatment. Neuraminidase inhibitors are therefore used almost exclusively. But even for this class of drugs, numerous cases of resistance have already been described. In 2009, over 90% of seasonally circulating H1N1 influenza viruses were resistant to oseltamivir. In addition to rising resistance, the emergence of a novel pandemic virus also poses a major threat.

The long-term goal of the project is therefore to make a far-reaching contribution to the development of novel agents for the treatment of influenza infections. The long-term goal of the project is therefore to make a far-reaching contribution to the development of novel agents for the treatment of influenza infections. To identify novel compounds, we analyze antimicrobial peptides, toxins and microbial extracts from the IME-BR strain collection by screening assays. Identified leads will be evaluated for their antiviral efficiency against different influenza subtypes in both immortalized cell lines and a primary lung cell model. In addition, the resistance profile of the leads as well as the efficacy in a combination therapy are investigated. Besides, the toxicity of the compounds will be determined first in cell culture models and, for promising compounds, in a Galleria mellonella model. Finally, the most effective compound will be investigated about its toxicity, pharmacokinetic properties and its effect in an infection model in laboratory mice.