The host cell's molecular arsenal is used by viruses to multiply. This is something that researchers from the University of Bonn's Cluster of Excellence ImmunoSensation2 and their Japanese counterparts hope to take advantage of for the treatment of influenza.
The team at the University Hospital Bonn under the direction of Prof. Hiroki Kato has discovered a substance that blocks the body's own methyltransferase MTr1, which prevents the spread of influenza viruses. The substance demonstrated synergistic effects with currently licensed influenza medicines and was effective in animal experiments and lung tissue preparations. The work has now been released in the Science publication.
To replicate, viruses need a host cell. There they introduce their genetic information in the form of the nucleic acids DNA or RNA. These molecular blueprints are used in the host cell to produce new viruses. In order to distinguish foreign from its own nucleic acids, the cell uses a kind of labeling system. Own RNA, for example, is tagged with a molecular cap that identifies it as non-hazardous. This enables the immune system to react specifically to threats.
The molecular cap is a methylated nucleoside: A small molecule attached to the end of the RNA chain. Tagged in this way, the RNA does not trigger an immune response. However, if there is RNA in the cell that lacks the cap structure, it is recognized by the immune receptor RIG-I, and the immune system is alerted. To escape this, influenza viruses have developed a special mechanism. They steal the molecular cap from cellular RNA molecules and transfer it to their own RNA. This process is called cap-snatching.
The researchers want to harness this dependence for the treatment of influenza infections. To this end, they searched for inhibitors that specifically inhibit MTr1. The team investigated how the substances in the infected tissue affect the number of virus particles produced. The researchers tested this both in mouse models and in human lung tissue preparations. These so-called lung explants come from patients who have undergone lung surgery. "Among thousands of candidates, we were able to identify a molecule that inhibits MTr1 in human lung explants and also in vivo in mice, curtailing influenza replication," reports Prof. Hiroki Kato, a member of the Cluster of Excellence ImmunoSensation2 at the University of Bonn.
The inhibitor is a derivative of a natural product called trifluoromethyl tubercidin (TFMT), which is produced by bacteria of the genus Streptomyces. "We hope this study will lead to the development of new treatments for influenza," says Prof. Hiroki Kato. In the present study, the researchers were already able to demonstrate that TFMT works together with approved drugs against influenza infections. It was even possible to show a clear synergistic effect with regard to the number of virus particles produced in the tissue.
( With inputs from ANI )
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