SARS-CoV-2 vulnerability discovered
Although there are now several vaccines against the coronavirus SARS-CoV-2 or the disease COVID-19 caused by the pathogen, there is still no effective therapy against the disease despite intensive research in numerous scientific institutes worldwide. However, researchers from Germany have now discovered a new weak point in the virus that could be used for drug development.
The first vaccination programs against SARS-CoV-2 have started in various countries. It is expected that more vaccines will be approved in the coming weeks and months. However, hopes are also aimed at finding drugs to treat those who are already infected. The discovery of German researchers could help: they have identified a new vulnerability in the coronavirus.
Weak point discovered with a new approach
The search for effective antiviral agents against the SARS-CoV-2 coronavirus is in full swing. As the German Center for Infection Research (DZIF) in a current Message writes, Tübingen researchers have now used a novel approach to discover a weak point in the virus that could be used for drug development. The team’s results were published in the journal “Bioinformatics” released.
Virus could no longer multiply
In a computer model, DZIF scientist Andreas Dräger and his team identified a human enzyme that is crucial for the pathogen. If it was switched off in the model, the corona virus could no longer multiply.
“When we switched off the enzyme – guanylate kinase 1 – the virus stopped replicating without affecting the host cell,” explains Dr. Andreas Dräger. With a junior professorship at the DZIF at the University of Tübingen, Dräger operates computer-based systems biology and started corona research with his team in January.
For their approach, the bioinformaticians developed an integrated computer model with the novel coronavirus SARS-CoV-2 and human alveolar macrophages. The latter are responsible for the defense against foreign substances in the alveoli.
“There was already a complex computer model for these macrophages that we were able to further develop for this purpose,” explains Dräger.
Research without cells and laboratory animals
The initial situation in the model was that the coronavirus had penetrated the host, here the human alveolar macrophage, and had already reprogrammed it. “Biochemical reactions that the virus uses in the host are already integrated into the model,” says Dräger.
The model now assumes that the pathogen wants to produce new virus particles and spread. To do this, the virus uses materials from the host and forces the host cells to produce new virus components.
“We first analyzed the composition of the virus and then calculated what material is needed to produce a virus particle,” says the expert, describing the procedure. And: “If you know that, you can run through various scenarios and see how the biochemical reactions in the host cells change during a virus infection.”
Possible point of attack of antiviral agents
In so-called flow balance analyzes, the Tübingen scientists then systematically tested which biochemical reactions take place differently in infected cells than in non-infected cells.
The researchers were able to start their further experiments with these reactions. By specifically switching off the selected reactions, they tracked down the processes that are particularly important for the coronavirus. For example guanylate kinase (GK1), which completely stopped the pathogen from multiplying when switched off.
According to the information, GK1 is also important in other viral diseases. According to the announcement, the enzyme that occurs in alveolar macrophages plays an important role in the metabolism of the building blocks of ribonucleic acids (RNA) and is therefore also significantly involved in the structure of viral RNA, such as that of SARS-CoV-2.
“While virus replication no longer takes place without GK1, the human cell can switch to other biochemical metabolic pathways,” says Dräger. However, this is an important prerequisite if you want to inhibit the enzyme with an active ingredient without causing adverse side effects in humans.
Some inhibitors of the enzyme are already known and the researchers from the University of Tübingen are now planning to work with their Hamburg cooperation partner Dr. Bernhard Ellinger from the Fraunhofer IME ScreeningPort (IME) to test already approved inhibitors for their effectiveness against the new coronavirus. (ad)
Author and source information
This text complies with the requirements of specialist medical literature, medical guidelines and current studies and has been checked by medical professionals.
- German Center for Infection Research (DZIF): SARS-CoV-2: Bioinformaticians discover a new weak point of the virus, (accessed: 04.01.2021), German Center for Infection Research (DZIF)
- Alina Renz, Lina Widerspick, Andreas Dräger: FBA reveals guanylate kinase as a potential target for antiviral therapies against SARS-CoV-2; in: Bioinformatics, (veröffentlicht: 29.12.2020), Bioinformatics
This article is for general guidance only and should not be used for self-diagnosis or self-treatment. He can not substitute a visit at the doctor.