New protein target to help fight flu

Researchers, including those of Indian-origin, have identified host protein molecules that could be blocked to prevent flu viruses from multiplying effectively, paving the way for a new therapeutic strategy to treat influenza.
In recent years, influenza A viruses (IAV) have been discovered that are resistant to current drugs against flu.
The flu is triggered by infections with influenza viruses, which multiply heavily in the respiratory tract. In order to replicate within the cells of the respiratory tract, the viruses rely on host molecules.
In recent years, there have thus been attempts to identify and block key host molecules for this process in order to stop the virus in its tracks.

An international team of researchers, including Shashank Tripathi from Icahn School of Medicine at Mount Sinai in US, analysed datasets from independent publications on IAV host molecules.
These studies focus on the totality of the genes ('GenOMICs') and proteins ('ProteOMICs') required for the virus and generate a vast quantity of data.

Thanks to the comprehensive analysis of these 'OMIC' databases, 20 previously unknown host molecules that promote the growth of influenza A viruses have been discovered.
"These unchangeable host proteins are vital for the replication of the viruses," said Silke Stertz, professor at the University of Zurich.
"One of these host proteins is UBR4, which the virus needs to transport viral proteins to the cell membrane and construct new particles," he said.

"The influenza A virus invades the host cell. The viral components are then carried to the cell surface, where they form new viruses. Consequently, as many as 20,000 new influenza viruses can develop from one, single infected host cell," he said.
The study shows that blocking UBR4 inhibits the production of new virus particles in infected cells. In mice, for instance, the IAV replication could be weakened and the progress of the disease slowed.
The study therefore provides evidence that blocking host molecules is feasible as a therapeutic strategy for the treatment of influenza.
The research team created a simplified, user-friendly web portal on influenza and host interaction. The site is also accessible to other researchers, enables individual requests and provides analysis tools to trace host proteins that are probably involved in the flu infection.

As a result, the data published may help develop the next generation of influenza medication, researchers said.
"We expect the approach described in this study and the use of 'big data' to bridge the gap between biomedical research and therapeutic development, and facilitate fresh insights into previously unanswered medical questions," said co-author Sumit Chanda from Sanford Burnham Prebys Medical Discovery Institute (SBP) in California.