22-Jul-2021 - Johann Wolfgang Goethe-Universität Frankfurt (Main)

SARS-CoV-2: Achilles’ heel of viral RNA

Several small molecules identified that bind to certain areas of the SARS-CoV-2 genome that are almost never altered by mutations

Certain regions of the SARS-CoV-2 genome might be a suitable target for future drugs. This is what researchers at Goethe University, together with their collaborators in the international COVID-19-NMR consortium, have now discovered. With the help of dedicated substance libraries, they have identified several small molecules that bind to certain areas of the SARS-CoV-2 genome that are almost never altered by mutations.

When SARS-CoV-2 infects a cell, it introduces its RNA into it and re-programmes it in such a way that the cell first produces viral proteins and then whole viral particles. In the search for active substances against SARS-CoV-2, researchers have so far mostly concentrated on the viral proteins and on blocking them, since this promises to prevent, or at least slow down, replication. But attacking the viral genome, a long RNA molecule, might also stop or slow down viral replication.

The scientists in the COVID-19-NMR consortium, which is coordinated by Professor Harald Schwalbe from the Institute of Organic Chemistry and Chemical Biology at Goethe University, have now completed an important first step in the development of such a new class of SARS-CoV-2 drugs. They have identified 15 short segments of the SARS-CoV-2 genome that are very similar in various coronaviruses and are known to perform essential regulatory functions. In the course of 2020 too, these segments were very rarely affected by mutations.

The researchers let a substance library of 768 small, chemically simple molecules interact with the 15 RNA segments and analysed the result by means of NMR spectroscopy. In NMR spectroscopy, molecules are first labelled with special types of atoms (stable isotopes) and then exposed to a strong magnetic field. The atomic nuclei are excited by means of a short radio frequency pulse and emit a frequency spectrum, with the help of which it is possible to determine the RNA and protein structure and how and where small molecules bind.

This enabled the research team led by Professor Schwalbe to identify 69 small molecules that bound to 13 of the 15 RNA segments. Professor Harald Schwalbe: “Three of the molecules even bind specifically to just one RNA segment. Through this, we were able to show that the SARS-CoV-2 RNA is highly suitable as a potential target structure for drugs. In view of the large number of SARS-CoV-2 mutations, such conservative RNA segments, like the ones we’ve identified, are particularly interesting for developing potential inhibitors. And since the viral RNA accounts for up to two thirds of all RNA in an infected cell, we should be able to disrupt viral replication on a considerable scale by using suitable molecules.” Against this background, Schwalbe continues, the researchers have now already started follow-up trials with readily available substances that are chemically similar to the binding partners from the substance library.

Facts, background information, dossiers

  • SARS-CoV-2
  • coronaviruses
  • Covid-19

More about Uni Frankfurt am Main

  • News

    Pharmaceutical research: when active substance and target protein “embrace” each other

    Scientists at Goethe University Frankfurt, together with colleagues from Darmstadt, Heidelberg, Oxford and Dundee (UK), have investigated how the fit of potent inhibitors to their binding sites can be optimised so that they engage longer with their target proteins. Long target residency has ... more

    Folding of SARS-CoV2 genome reveals drug targets

    For the first time, an international research alliance has observed the RNA folding structures of the SARS-CoV2 genome with which the virus controls the infection process. Since these structures are very similar among various beta corona viruses, the scientists not only laid the foundation ... more

    Possible Achilles’ heel of SARS-CoV-2 virus identified

    When the SARS-CoV-2 virus penetrates human cells, it lets the human host cell produce proteins for it. One of these viral proteins, called PLpro, is essential for the replication and rapid spread of the virus. An international team of researchers led by Goethe University and University Hosp ... more

  • q&more articles

    From feast to famine and back – no problem for bacteria

    Bacteria are true survivors. In the course of evolution, they have developed numerous strategies to adapt to rapidly changing, uncertain environmental conditions. Their metabolism is much more sophisticated than that of human beings. Within minutes they can regulate their gene expression an ... more

    Why biosimilars and not biogenerics?

    Medicines produced using genetic techniques have existed since 2006, called “similar biological medicinal products” or “biosimilars”. Until a year ago, this was a fairly low-profile group, even in expert circles. This has all changed now, however, with the recent licensing of the first bios ... more

    Paradigm shift

    What would medicine be without drugs? But are these drugs being used optimally today? Not at all, as we now know thanks to the findings of molecular medicine. Because for the use of these drugs, it is important to observe two aspects: the disease and the patient. Only slowly is it becom ... more

  • Authors

    Prof. Dr. Jörg Soppa

    Jörg Soppa, born in 1958, studied biochemistry in Tübingen and then went on to do his doctorate at the Max Planck Institute of Biochemistry in Martinsried near Munich. In 1990 he established his own research group there and held courses at the Institute of Genetics and Microbiology of Munic ... more

    Prof. Dr. Heinfried H. Radeke

    Heinfried H. Radeke studied medicine at the Hannover Medical School (MHH) and received his medical license in 1985. His Ph.D. thesis was recognized as the best research dissertation of 1986. After two years as an assistant physician at the Göttingen University Hospital, he began his career ... more

    Prof. Dr. Theo Dingermann

    Theodor Dingermann, born 1948, studied pharmacy in Erlangen ­and received his doctor title in 1980 to become Dr. rer. nat. In 1990 he was offered the C4 professorship at the Institute for Pharmaceutical Biology, University of Frankfurt.  From 2000 to 2004 he was President of the German Phar ... more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by: