How coronaviruses hijack host cells and block the body’s own defenses
Despite years of research in relation to this Coronavirus SARS-CoV-2 and the disease caused by the pathogen COVID-19 still much unclear. Experts have now achieved a significant success. They have possible points of attack for the Antiviral Therapy discovered.
So far, there has been contradictory discussion in specialist circles as to how corona viruses manage to hijack host cells and thereby block the body’s own defences. Researchers led by Marina Chekulaeva from the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) have now decoded the key mechanism.
How SARS-CoV-2 takes over the cell’s protein factory
A little over two years have passed since the outbreak of the coronavirus SARS-CoV-2. In order to keep the pathogen in check and stop its pandemic spread, vaccines have so far mainly been available. However, these are currently not able to completely stop the transmission of the virus, according to a current one Message MDCs.
It is also to be expected that future virus variants will be modified in such a way that they can bypass the vaccine protection. It is therefore of great importance to better understand SARS-CoV-2 and the mechanisms by which it infects cells, manufactures its own protein molecules and finally produces new virus particles.
In this way, possible points of attack for the targeted therapy of an infection with the coronavirus can be found.
A team around Dr. Marina Chekulaeva at the Berlin Institute for Medical Systems Biology (BIMSB) of the MDC, together with researchers from the Leibniz Institute for Analytical Sciences in Dortmund, discovered how the virus takes over the cell’s protein factory – to synthesize viral proteins while at the same time producing the body’s own to block proteins and thus overturn the immune response of the host cell.
In the journal “RNAThe scientists present their results.
Targeting viral protein
In this context, researchers have long had their sights set on a viral protein with the acronym NSP1. This is the first virus protein to be made following infecting the host cell. “NSP1 suppresses the cell’s protein production without affecting the synthesis of viral proteins”explains Chekulaeva.
“So far, there have been very contradictory hypotheses regarding how this can be achieved. We decided to explore this mechanism with Lucija Buinic, the first author of the manuscript.”
The team managed to uncover this process. It was already known that the NSP1 protein attaches itself to the ribosomes, which serve as the cell’s protein factories. More specifically, it anchors itself in the tunnel through which messenger RNA (mRNA) enters the ribosome so that the blueprint can be read and ultimately translated into proteins.
As a result, the ribosome is virtually blocked: cellular mRNAs can no longer reach the protein factory, and the synthesis of important cellular protein molecules in the cell cannot take place. Ultimately, this also affects the immune response, which is suppressed in this way.
Hairpin structure seems to serve as a pass
However, viral mRNAs also need access to the protein factories so that new virus particles can ultimately develop. But how do they bypass the blockage that caused the virus?
The researchers found that certain nucleotides in a special structure of the viral mRNA, the so-called hairpin or stem loop, play a role. According to the experts, this hairpin seems to serve as a kind of pass: it interacts with NSP1, which in turn opens the way into the ribosome. The viral protein can be synthesized.
“We have thus discovered three possible targets for antiviral therapy”, says Chekulaeva. One possibility would be to attack the NSP1 protein itself so that it cannot interact with the ribosome.
Alternatively, the interaction between the NSP1 protein and the viral mRNA might also be prevented. For example, the point at which NSP1 interacts with the hairpin structure might be blocked.
It would also be conceivable to specifically eliminate viral mRNA. For this purpose, the research team has produced chemically modified and thus stabilized oligonucleotides that attach themselves to the hairpin structure. This creates an RNA-DNA hybrid that is eliminated from the cell.
Because this hairpin structure is specific for viral mRNA, such an intervention is very specific – the cellular mRNA and thus the protein synthesis of the infected cell are not affected.
“It’s also a very important structure that we have a high probability of not mutating at all.”so Chekulaeva. “The development of resistance would therefore be rather unlikely.”
At least in the experiment in the culture dish, all three possibilities are conceivable. Future studies will have to show which of these is ultimately suitable for therapy. (ad)
Author and source information
This text corresponds to the specifications of medical specialist literature, medical guidelines and current studies and has been checked by medical professionals.
Swell:
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association: How SARS-CoV-2 hijacks the cell’s protein factory, (accessed: March 13, 2022), Max Delbrück Center for Molecular Medicine in the Helmholtz Association
- Lucija Bujanic et al.: The key features of SARS-CoV-2 leader and NSP1 required for viral escape of NSP1-mediated repression; in: RNA, (veröffentlicht: 01.03.2022), RNA
Important NOTE:
This article contains general advice only and should not be used for self-diagnosis or treatment. He can not substitute a visit at the doctor.
