New target structure against coronavirus

Quite unexpectedly, the enzyme ceramidase emerges as a new target structure for the treatment of SARS-CoV-2 infection. This is reported by the Würzburg researchers in the journal Cells,

Fluoxetine, a common antidepressant, inhibits SARS-CoV-2 coronavirus in cell cultures and in preparations from human lung tissue. It was demonstrated in the summer of 2020 by researchers from the Julius-Maximilians-Universitat (JMU) Würzburg. However, the mechanism of this inhibition was not completely clear, so the teams continued their research.

For this, they developed the molecule AKS466, which is similar to fluoxetine and also suppresses the coronavirus. After an extensive comparative study published in the scientific journal CellsIt is now clear how antidepressants inhibit the replication of the coronavirus.

Overexpression of ceramides inhibits SARS-CoV-2

Fluoxetine, as well as AKS466, trap the virus in the cell’s lysosome. Simply put; These are small vesicles that contain digestive functions. In lysosomes, both active substances also suppress the activity of an enzyme group, acid ceramidase. This increases the concentration of ceramides, a group of lipids in the body. The excess of ceramides is ultimately responsible for preventing the SARS-CoV-2 coronavirus from reproducing.

“The enzyme ceramidase is a new, completely unexpected target structure for antiviral therapy,” says Professor Jochen Bodem from the JMU Institute of Virology and Immunobiology. His group collaborated closely with the teams of JMU professors Jürgen Seibel (Organic Chemistry) and Marcus Sauer (Biotechnology and Biophysics) on this project. The work was funded by the pharmaceutical company Novartis and the Free State of Bavaria.

medical research results

The new findings are important for the fight against SARS-CoV-2.

On the one hand, ceramides may be directly suitable as active agents against viruses.

On the other hand, a fluoxetine-like molecule AKS466 may be superior to the original. This is because fluoxetine inhibits the enzyme group of acid sphingomyelinase, the use of which causes side effects. AKS466 does not inhibit these enzymes – it should have fewer adverse side effects.

Thus, the Würzburg researchers are showing two new ways to better treat SARS-CoV-2 infections. Next, they would like to clarify the question of how the two active substances manage to trap the coronavirus in the lysosome.

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material provided by University of Würzburg, Original written by Robert Emmerich. Note: Content can be edited for style and length.