Bonn Pharmaceutical scientists at the University of Bonn have now discovered that two active substances could slow down the coronavirus. These probably block an enzyme of the virus that is crucial for its reproduction.
Pharmaceutical scientists at the University of Bonn have found a new, promising approach in the search for treatments against Sars-CoV-2. They have discovered two groups of active substances that can block the replication of the coronavirus in the body. According to initial results, the two contenders appear to block the "major protease" - an enzyme of the virus that is crucial for its replication. According to the university, the results were obtained in a laboratory, so this is basic research that now needs to be supplemented by clinical trials. The study has been published in the journal "Angewandte Chemie".
In order for the coronavirus to replicate, it first produces a cluster of different proteins. The main protease separates these proteins from each other so that they can be turned into the "replication complex," the virus's self-copying machine. The approach is: main protease deactivated = virus copier deactivated.
“An extremely promising starting point”
"The main protease is an extremely promising starting point for coronavirus drug research," says Professor Christa E. Müller of the university's Pharmaceutical Institute. "If this enzyme is blocked, then virus replication in the body's cells is stopped." The renowned scientist is a member of the university's interdisciplinary research area "Life and Health.”
Based on the known structure of the virus, the researchers first designed a number of substances that seemed suitable for blocking the main protease. "The condition for a suitable inhibitor is that it binds sufficiently tightly to the main protease and can block its active site," explains Professor Michael Gütschow, head of a separate working group at the Pharmaceutical Institute on such "inhibitors" (= inhibitors).
The researchers then tested the effects of the potential inhibitors in a mass testing process and in this testing, the protease virtually told the researchers itself whether it was blocked: A second substance was added to the active ingredient to be tested, combined from different molecules. When the protease did its job (i.e., broke down the molecules), one of them produced a molecule that prompted a “flash of light” that could be detected in the laboratory. Conversely, if this fluorescence did not occur, it meant that the substance being tested had switched off the protease.
"For most of the test compounds, we observed no enzyme inhibition," says Gütschow. "But in rare cases in our extensive testing, fluorescence was suppressed: these were the hits we were hoping for in our search for viral protease inhibitors.”
Extensive clinical testing still needed
Two classes of compounds are particularly promising, according to the researchers' findings; the experts developed tailored compounds from them that stick to the main protease like chewing gum. They block the enzyme's "catalytic center," the crucial part on which its entire function depends - including the replication of the virus.
"Some of the compounds have another effect," Müller said. "They inhibit a human enzyme that helps the virus enter body cells." But as mentioned, at the moment, all of this only works in the lab. Whether the drug contenders designed in this way also inhibit the reproduction of the coronavirus in humans remains to be proven in extensive clinical tests.
(Orig. text: Margit Warken-Dieke, Wolfgang Pichler / Translation: Carol Kloeppel)