How the coronavirus multiplies its genetic material

idw – Informationsdienst Wissenschaft

Nachrichten, Termine, Experten

Grafik: idw-Logo
Thema Corona

idw-Abo
Science Video Project



Share on: 
04/28/2020 11:58

How the coronavirus multiplies its genetic material

Dr. Carmen Rotte Presse- und Öffentlichkeitsarbeit
Max-Planck-Institut für biophysikalische Chemie

    When someone becomes infected with the novel coronavirus SARS-CoV-2, the pathogen proliferates rapidly in the cells of the infected person. To do so, the virus has to multiply its genetic material, which consists of a single long RNA strand. This task is performed by the viral 'copy machine', the so-called polymerase. Scientists led by Patrick Cramer at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, have now determined the 3D structure of the corona polymerase. This makes it possible to investigate how antiviral drugs such as remdesivir – which blocks the polymerase – work, and to search for new inhibitory substances.

    “In view of the current pandemic we wanted to help,” Max Planck Director Cramer says. “We have extensive experience in studying polymerases.” It was therefore obvious to the scientists what project to choose.

    “We were surprised to find that the structure of the coronavirus polymerase is special - it differs from other structures that we have been investigating so far,” explains Hauke Hillen. The coronavirus polymerase binds to the RNA in the same way as is known from other types of viruses. However, this polymerase comprises an additional element with which it binds the RNA until it has copied the genetic material. This is important for the corona virus as its genome consists of around 30,000 building blocks and is therefore particularly long, making copying a major challenge.

    Understanding in detail how antivirals work

    Knowing how the coronavirus polymerase is constructed on an atomic scale opens up new possibilities to better understand and combat the pathogen. In the next step, Cramer's team will investigate in detail how antiviral substances block the proliferation of coronaviruses. "Many hopes rest on remdesivir, which directly blocks the polymerase. With the structure at hand it might be possible to optimize existing substances such as remdesivir and to improve their effect. But we also want to search for new substances that are able to stop the virus polymerase,” Cramer says.

    The Göttingen researchers have already published their results in a manuscript on the internet. “We wanted to immediately share our findings with the international scientific community to speed things up, now that we are in the middle of the pandemic,” reports Lucas Farnung, who will soon take up a professorship at Harvard University in the United States.

    Corona polymerase at 100,000-fold magnification

    The path to the three-dimensional structure of the corona polymerase was rocky. “First, we had to reconstitute the polymerase from three purified proteins. After some optimization, it was finally functional in the test tube,” explains Goran Kokic. “Only then we were able to study how it works.” To do so, the scientist had quickly established a special test to determine the activity of the polymerase.

    The team then examined the samples in the electron microscope with a magnification of more than 100,000-fold – and at first disappointment set in: “Although we took pictures around the clock for ten days and nights, we were unable to gain detailed insights into the structure,” recalls Christian Dienemann, an expert in electron microscopy. “However, one sample looked different, somehow strange. Our first thought was to discard it. Fortunately, we did not: This sample, over all, provided us with the high-quality data we needed,” says Dimitry Tegunov, the group's data processing expert who also programmed the software to process large volumes of image data in a short time.

    The determination of the polymerase structure will not be the last contribution of the Göttingen researchers to tackling the pandemic: “We are planning to take a look at the helper factors that change the viral RNA in such a way that it cannot be degraded by the human immune system,” Cramer says. “And of course, as structural biologists, we hope to find further targets in the virus that might open up new therapeutic strategies in the medium term.”


    Contact for scientific information:

    Prof. Dr. Patrick Cramer, Department of Molecular Biology
    Max Planck Institute for Biophysical Chemistry
    Phone: +49 551 201-2800
    E-Mail: patrick.cramer@mpibpc.mpg.de


    Original publication:

    Hillen HS*, Kokic G*, Farnung L*, Dienemann C*, Tegunov D*, Cramer P*
    (*equal contribution): Structure of replicating SARS-CoV-2 polymerase. Link to online pre-publication: https://www.biorxiv.org/content/10.1101/2020.04.27.063180v1


    More information:

    https://www.mpibpc.mpg.de/17275755/pr_2008 - Original press release of the Max Planck Institute for Biophysical Chemistry
    https://www.mpibpc.mpg.de/cramer – Website of the Department of Molecular Biology of Patrick Cramer, Max Planck Institute for Biophysical Chemistry


    Attachment
    attachment icon 3D view of the coronavirus polymerase: The genetic material (RNA) is depicted in blue and red.

    Criteria of this press release:
    Journalists, Scientists and scholars, Students, all interested persons
    Biology, Chemistry, Medicine
    transregional, national
    Research results, Scientific Publications
    English


    The polymerase of the new coronavirus SARS-CoV-2 multiplies the pathogen's genetic material (blue and red).


    For download

    x

    Help

    Search / advanced search of the idw archives
    Combination of search terms

    You can combine search terms with and, or and/or not, e.g. Philo not logy.

    Brackets

    You can use brackets to separate combinations from each other, e.g. (Philo not logy) or (Psycho and logy).

    Phrases

    Coherent groups of words will be located as complete phrases if you put them into quotation marks, e.g. “Federal Republic of Germany”.

    Selection criteria

    You can also use the advanced search without entering search terms. It will then follow the criteria you have selected (e.g. country or subject area).

    If you have not selected any criteria in a given category, the entire category will be searched (e.g. all subject areas or all countries).

    Cookies optimize the use of our services. By surfing on idw-online.de you agree to the use of cookies. Data Confidentiality Statement
    Okay