Since the Corona pandemic, one question has been driving research: How can a virus that is constantly changing be slowed down? Vaccines protect against severe progression. There are also specific therapies. But a broadly effective drug against the coronavirus is still missing. A new study now shows a possible way out – and surprisingly, it lies in our own cells.

The work was published in the specialist journal “Nature Communications“. The Pompeu Fabra University in Barcelona was in charge under the direction of molecular virologist Juana Díez. “Coronaviruses are very dangerous because of their ability to generate new variants that, after circulating in animal reservoirs, can infect humans,” says Díez. “We currently have no broadly effective antiviral drugs against coronaviruses.”

Her team therefore investigated how the viruses control the protein production of infected cells – and how this mechanism can be specifically disrupted.

Coronaviruses specifically reprogram cells

Coronaviruses bring your own building instructions. This results in up to 32 virus proteins. They rely entirely on human cellular machinery for their production. Without these “production halls” they would not be able to multiply.

The virus actually needs to be slowed down during the production of its proteins. Because many of its genetic building blocks are considered more difficult for human cells to read. Nevertheless, production runs surprisingly quickly. This is where the study started.

Stress becomes an advantage for the coronavirus

It starts with a stress reaction. When coronaviruses infect a cell, it comes under pressure. The researchers were able to observe this in lung cells: certain warning signals increased significantly. This stress situation in turn changes enzymes in the cell.

And this is where it becomes crucial. These enzymes control tiny helpers called tRNAs. They bring the building blocks for new proteins to the right place – similar to suppliers in a production chain.

“Interestingly need Coronaviruses tRNAs, which are only present in small amounts in cells. That’s why we asked ourselves how a virus can spread so quickly in a cell in which the required tRNAs are not abundant,” explains lead author Elena Muscolino.

The answer was surprisingly simple: the virus no longer produces these helpers. It changes their properties. This means that exactly the building instructions that the virus needs are implemented with priority. So the cell doesn’t work faster – it works differently. The virus fine-tunes production so that its own components are created more quickly.

Prospect for a new coronavirus drug

The effect was particularly clear with targeted interventions. The scientists switched off individual cellular helpers or changed their activity. As soon as these processes were slowed down, the amount of virus components formed fell noticeably. The virus lost momentum.

A future active ingredient could take advantage of this mechanism: “A tRNA-modifying enzyme is a promising candidate for the development of broadly effective antiviral drugs that can curb the spread of coronaviruses,” says Díez.

The idea behind it is simple but effective: Instead of attacking the virus directly, a drug could block the cellular processes that the virus uses to multiply. That would be strategically interesting. Because different coronaviruses seem to use the same mechanism. Such an approach could therefore have a broader effect than many previous therapies.

“A drug of this type would make it possible to contain infections caused by new coronaviruses in early phases and prevent their rapid spread,” explains the head of the study.

Confirmation in animal models

The researchers also checked their results on infected golden hamsters. Two days after the infection, they examined the lung tissue. Certain chemical changes were significantly increased, especially when the amount of virus was high.

The mechanism works not only in cell cultures in the laboratory, but also in living organisms. There is still no finished preparation. But the study describes a clear target in our own cells – and thus a realistic basis for a broadly effective drug against coronaviruses.

Briefly summarized:

• Coronaviruses not only use the cell machinery, but also specifically change it so that their own virus components are produced more quickly.
• To do this, they change little helpers in the cell instead of building new structures – if this process is blocked, virus production drops significantly.
• A future drug could inhibit precisely these cellular helpers and thus slow down various coronaviruses before they spread en masse.

By Sina Trepte