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Infections - Fighting the Chikungunya virus

Chikungunya-Virus (yellow) (Picture: InstitutPasteur, T. Coudercund M. Lecuit)

Scientists have developed a new strategy for the search on therapeutic options against Chikungunya. They have identified both known agents, as well as a new class of compounds as potential antiviral drugs.

 

Originating from the tropical range, the Chikungunya virus has spread increasingly to the north in recent years, and already reached the southern United States. In Europe, a number of regional outbreaks have been documented. The virus, which is transmitted by the Asian tiger mosquito, triggers flu-like symptoms that can last for months and in rare cases can be fatal. Currently there is no vaccine or an approved drug against Chikungunya. An international team of scientists, including the LMU pharmacist Franz Bracher, now presented a new strategy in the Nature Communications journal, by which new treatment options can be established faster than before, and identified appropriate agents.

To propagate, all pathogens need certain proteins that are formed by the host cell. In a first step, a group of researchers including Thomas F. Meyer (Max Planck Institute for Infection Biology) identifed the proteins which the virus absolutely requires for replication in infected human host cells, by using a genome-wide screening. For this purpose, the researchers switched off each individual gene of the human cells in a complex automated process, infected the modified cells, and then analyzed the extent of virus replication. This enabled them to identify more than 100 human proteins that are essential for the replication of the virus. In cooperation with virologists including Marc Lecuit of the Institut Pasteur (Paris), as well as researchers from the Charité and the Steinbeis Innovation Center in Berlin, the Institute of Technology in Tartu, Estonia, and Bracher's research group at the Department of Pharmacy, the scientists identified the substances which can control these important human proteins and thus inhibit the replication of the virus. „This includes both drugs that have already been used for the therapy of other diseases, but had not been considered for the treatment of viral infections previously, as well as novel small molecules, such as so-called inhibitors of protein kinase CLK1, which were synthesized in our laboratory" says Bracher.

According to the first findings of the researchers, it is particularly encouraging that this principle may be transferred to other pathogenic viruses. „With this innovative approach, on one hand, it is possible to identify well-known, well-characterized agents from other therapeutic areas for new therapeutic challenges in infectious diseases, which could then be introduced relatively quickly as anti-infectives on the market,” says Bracher, "on the other hand, it might be possible that completely new classes of compounds could be identified as potential drugs, as it was the case with our kinase inhibitors.”

Nature Communications 2016