• Phage shell docks with the influenza virus.

    Berlin research alliance develops influenza inhibitor

Using viruses against influenza, avian flu - and maybe soon also against Corona? An alliance of scientists from the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), the Freie Universität Berlin (FU), the Technische Universität Berlin (TU), the Humboldt-Universität zu Berlin (HU), the Robert Koch Institute (RKI) and the Charité-Universitätsmedizin Berlin has developed a chemically modified  phage capsid in the Brain City Berlin, which makes flu viruses harmless by encapsulating them. Whether this groundbreaking development is also effective in humans will be investigated in the next step.

Influenza viruses are not only highly dangerous, they are also difficult to combat. The problem: Antiviral drugs used up to now only attack the virus when it has already infected the lung cells. This could change soon. As the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), announced on Monday, a multidisciplinary research alliance of scientists from the FMP, the Freie Universität Berlin (FU), the Technische Universität Berlin (TU), the Humboldt-Universität zu Berlin (HU), the Robert Koch Institute (RKI) and Charité-Universitätsmedizin Berlin has developed a groundbreaking approach to combat seasonal influenza and avian flu, which could possibly also be used against the coronavirus.

The interdisciplinary project is one of the most recent examples of successful, cross-institutional collaboration between scientific institutions in the Brain City Berlin. Just as the science location, the Berlin research alliance is characterized by on an open research atmosphere and a wide range of expert knowledge.

Like a Velcro tape - that is how the new approach works

The inhibitor, developed jointly by biologists, chemists, physicists, virologists, medical doctors and imaging specialists, makes use of a characteristic that all influenza viruses have: On their surfaces there are three-binding (trivalent) receptors, the so-called haemagglutinin proteins. In the case of infection, the viruses hook into the lung cells - similar to a Velcro fastener. The core principle of the new inhibitor: It “deceives” the flu virus by simulating the surface of lung tissue cells. 

The active ingredient is based on a harmless intestinal inhabitant: a so-called “Q-beta phage”. Phages are viruses that use bacteria or other viruses as hosts and thus render them harmless. Based on an empty and therefore non-infectious shell of such a phage, the Berlin researchers developed a chemically modified “phage capsid”. This empty phage shell encapsulates the influenza viruses perfectly and literally takes the air to breathe away from them. To provide “bait” for the virus, sugar molecules are attached to the phages.  

The approach of the Berlin research alliance offers completely new perspectives for the development of antiviral drugs. “Pre-clinical trials show that we are able to render harmless both seasonal influenza viruses and avian flu viruses harmless with our chemically modified phage shell,” explains Professor Dr. Christian Hackenberger, Head of the Department Chemical Biology at the FMP and Leibniz-Humboldt Professor for Chemical Biology at HU Berlin. “Our rationally developed, three-dimensional, multivalent inhibitor points to a new direction in the development of structurally adaptable influenza virus binders. This is the first achievement of its kind in multivalency research.” 

Preclinical studies are expected to test the effectiveness in humans

Whether the new inhibitor will also work in humans, is what the Berlin researchers now want to test in further preclinical studies. The Berlin researchers confirm that the new approach has great potential. The inhibitor is biodegradable and non-toxic. Furthermore, in cell culture studies it proved not to be immunogenic; it caused no immune system response.

With the support of the Robert Koch Institute, the Berlin researchers were also able to investigate the potential of phage capsids against many current influenza virus strains and avian influenza viruses. And at the the Medical Department, Division of Infectiology and Pneumology, of Charité, the therapeutic potential of the inhibitor could be demonstrated in human lung tissue: If the tissue was infected with influenza viruses and treated with the phage capsid, the influenza viruses were practically unable to reproduce. 

In principle, the active ingredient can also be applied to other viruses, and possibly to bacteria, says Christian Hackenberger. Combating corona represents a new challenge for the Berlin researchers. They are currently pursuing the idea, by means of the phage approach, of developing an active ingredient that prevents the viruses from binding to the host cells in the throat and the subsequent airways, and thus an infection of humans.(vdo)

In my opinion, such a complex project could only have been undertaken in Berlin, where there truly are experts for every issue.
                                   (Professor Dr. Andreas Herrmann, Head of Molecular Biophysics at Humboldt University zu Berlin) 


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