The search for “the” medicinal weapon against the corona virus continues. Remdesivir is also used as a drug in Europe with restrictions.
Göttingen – Although it slows down SARS-CoV-2 pathogens, it is not the ultimate stopper for its reproduction in human cells. Researchers from Göttingen and Würzburg have now clarified this. However, this result could help in the search for substances that could stop the corona virus from multiplying.
Remdesivir in any case delays the polymerase, i.e. the copying of the virus RNA and thus the replication in the body, but does not completely inhibit it, as the researchers from the Max Planck Institute for Biophysical Chemistry in Göttingen and the University of Würzburg recognized in experiments and in ” Nature Communications ”.
“After complicated investigations, we came to a simple conclusion,” says MPI Director Patrick Cramer. “Remdesivir hinders the work of the polymerase, but only after a certain delay. However, the drug does not completely stop the enzyme. “
Prof. Patrick Cramer
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Cramer and his team have been on the trail of the coronavirus for a long time and had noticed at the beginning of the pandemic how the coronavirus doubles its RNA genome. This is a mammoth task for the pathogen. This is because virus RNA consists of a chain of around 30,000 RNA building blocks and is therefore particularly long.
Remdesivir works because its structure is similar to RNA building blocks, ”explains Claudia Höbartner, Professor of Chemistry at the University of Würzburg. The RNA copier polymerase can be misled by this and builds the remdesivir substance into the growing RNA chain.
Another result of the biochemical investigations and observations on the cryo-electron microscope: The copying process pauses when the RNA chain has been extended by three more RNA components after the incorporation of Remdesivir. “The polymerase no longer allows a fourth building block. This is ensured by two Remdesivir atoms that hook onto a specific point on the polymerase. “
The RNA production is not completely blocked, however, “the polymerase often continues to work after an error has been corrected,” explains Goran Kokic, research assistant in Cramer’s laboratory, who started the decisive experiments with Hauke Hillen, Dimitry Tegunov, Christian Dienemann and Florian Seitz started.
Despite the new knowledge about the limited effects of remdesivir, it opens up new opportunities for researchers to fight the virus. “Because we know how Remdesivir inhibits corona polymerase, we can work on improving the substance and its effects,” says Patrick Cramer. In addition, the MPI researchers want to search for new substances that can stop the viral copying machine. The resulting effective drugs would alleviate the course of Covid 19.
Patrick Cramer, however, promotes the vaccination: “The vaccinations are essential to bring the pandemic under control.”Thomas Kopietz)
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