Researchers have provided evidence of influenza-causing modifications to the enzyme, which creates copies of the influenza virus genome, and, therefore, could be used to produce new medicines. The team of researchers at the University of Muenster, Germany, was able to provide evidence of 59 specific modifications to the polymerase of the influenza A virus, or, in other words, the decisive enzyme responsible for the production of copies of the virus genome.
According to the study, what is special about the modifications described in the study is that they are transmitted by proteins in the host cells – and, in contrast to virus proteins, they cannot mutate rapidly.
The modifications, therefore, represent a promising approach for the production of new medicines, the study published in the journal Nature Communications said. Every year, the influenza season presents a challenge to hospitals.
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Despite having been vaccinated, older people and patients with health problems in particular run a heightened risk of falling prey to a severe bout of influenza. What is especially insidious about influenza viruses is their ability to mutate rapidly, which makes them increasingly resilient to medicines.
For this reason, there is an urgent need for new active ingredients to be able to continue providing effective treatment for the illness in the future. The study is an important step in this direction, it said.
The influenza A virus polymerase (IAV polymerase) is a highly complex protein that has more than just one function. One of these is that after a structural change, it can also make copies of the virus genome, cRNA, and vRNA.
Without this “switch” of functions, the virus is not able to proliferate. As Dr Linda Brunotte and Dr Franziska Guenl and a team of colleagues now discovered, according to the study, the IAV polymerase needs proteins from the host cell to act as “molecular switches” and carry out its diverse functions.
These proteins are enzymes that dock so-called ubiquitin proteins onto specific places in the polymerase and, as a result, trigger the signal for the switch of functions, the study said. “We were able to produce a map showing 59 positions on the viral polymerase to which ubiquitin was attached through the host cell. These are completely new findings which reveal the Achilles’ heel of the influenza A virus,” explained Brunotte, who initiated the study.
This ubiquitination had a definite influence on the activity of the polymerase at 17 spots, the study said. Moreover, one specific position was discovered whose modification represents the signal for the conversion and the associated switch of functions in the polymerase, the study said.
As a result, Dr Guenl, the lead author of the study, is now looking ahead. “On the basis of our mapping of the ubiquitination, further studies can now research into which enzymes are specifically responsible for the modification of the IAV polymerase.
“Medicines which are directed against these enzymes would be resistant to mutations in influenza viruses, thus displaying great potential for future treatments,” said Guenl.
(With inputs from PTI)
