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Coronavirus multiplies rapidly in human cells


Coronavirus: How SARS-CoV-2 increases its genetic make-up

The mucous membranes of the mouth, nose and eyes are considered the gateway for the SARS-CoV-2 coronavirus. When a person becomes infected with the novel virus, the pathogen multiplies rapidly in its cells. Researchers have now found out how the coronavirus reproduces its genome.

There are numerous coronaviruses around the world that constantly infect people and usually only cause mild respiratory diseases. Infections with the SARS-CoV-2 coronavirus are also relatively harmless in many cases. However, the new pathogen can also cause a serious respiratory illness called COVID-19. A research team is now reporting on how the virus reproduces its genome.

Coronavirus genome consists of around 30,000 building blocks

If a person becomes infected with the novel coronavirus SARS-CoV-2, it multiplies rapidly in their cells. To do this, the pathogen has to reproduce its genetic makeup, which consists of a long strand of RNA. The viral "copying machine", called polymerase, takes on this task.

According to a recent report, scientists led by Patrick Cramer from the Max Planck Institute for Biophysical Chemistry in Göttingen have now decoded the spatial structure of the corona polymerase.

According to the information, it can be used to research how antiviral substances that block the polymerase work. One of them is Remdesivir, a promising ingredient in the development of new drugs against COVID-19. In addition, new drug candidates can be searched.

"In view of the current pandemic, we wanted to help," explains Max Planck Director Cramer. "We have extensive experience in studying polymerases." The research topic was therefore obvious to the experts.

"The most surprising thing for us was that the structure of the corona virus copying machine falls out of line because it differs from other polymerase structures," says Hauke ​​Hillen.

According to the scientists, the corona polymerase binds to the RNA as is known from other virus types, but this polymerase has another element with which it clings to the RNA until it has copied the genetic material.

This is particularly important for the corona virus, because its genome consists of around 30,000 building blocks and is therefore particularly long. Copying is a real mammoth task.

Findings quickly shared with international research community

Knowing how the coronavirus polymerase is built atom by atom opens up new opportunities to better understand and fight the virus. In the next step, the research team wants to investigate in detail how antiviral substances block the proliferation of coronaviruses.

“There is a lot of hope in Remdesivir, which directly blocks the corona polymerase. The polymerase structure could make it possible to optimize existing substances such as remdesivir and improve their effect. But we also want to find new substances that can stop the virus polymerase, ”explains Cramer.

The Göttingen researchers published their results in a manuscript on the preprint server bioRxiv. "We wanted to share our findings with the international research community immediately, because now that we are in the middle of the pandemic, things have to go very quickly," reports Lucas Farnung, who will soon be switching to a professorship at Harvard University in the United States .

Hope for new therapy strategies

As stated in the communication, the path to the three-dimensional structure of the corona polymerase was rocky. “First of all, we had to recreate the polymerase from three purified proteins in a test tube. After a few tweaks, it was finally functional, ”explains Goran Kokic. "This was the only way we could investigate how she works."

The researcher quickly established a special test to determine the activity of the polymerase.

The experts then examined the samples in the electron microscope at a magnification of more than 100,000 times - and at first disappointment spread: "Although we had taken pictures around the clock for ten days and nights, we were unable to gain a detailed insight into the structure," said Christian Dienemann, expert in electron microscopy.

“However, a sample looked different, somehow strange. Our first thought was to reject it. Fortunately, we didn't do that: it was this sample of all that provided us with the high-quality data we absolutely needed, ”explains Dimitry Tegunov, the group's data processing expert, who also programmed the software to quickly process large amounts of image data.

According to the information, the decoding of the polymerase structure should not be the last contribution of the Göttingen researchers to deal with the pandemic:

"We are also targeting the so-called helper factors that change the virus RNA so that it cannot be broken down by the human immune system," said Cramer. "And of course we, as structural biologists, hope to find other targets in the virus that will open up new therapeutic strategies in the medium term." (Ad)

Author and source information

This text corresponds to the requirements of the medical literature, medical guidelines and current studies and has been checked by medical doctors.

Swell:

  • Max Planck Institute for Biophysical Chemistry: How the coronavirus increases its genetic make-up (accessed: April 29, 2020), Max Planck Institute for Biophysical Chemistry
  • Hillen HS *, Kokic G *, Farnung L *, Dienemann C *, Tegunov D *, Cramer P * (* equivalent contribution): Structure of replicating SARS-CoV-2 polymerase; bioRxiv, (published: April 27th, 2020), bioRxiv


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