Fighting the flu with "big data"

BIG DATA Thanks to "big data", researchers have identified new molecules that play an important role in the replication of the influenza virus. If these host proteins are blocked, influenza viruses are less able to replicate. The international study involving the University of Zurich is thus helping to develop new therapies and flu drugs.Flu epidemics occur almost every year during the winter months. Occasionally, novel virus strains can even spread into global pandemics. In recent years, influenza A viruses (IAV) have been discovered that are resistant to the flu treatment drugs available due to mutations. Influenza is caused by infections with influenza viruses that multiply rapidly in the respiratory tract. The viruses are dependent on host molecules in order to replicate within respiratory cells. For this reason, attempts have been made in recent years to identify and block the host molecules that are important for this process in order to stop the virus.Inhibition of host proteins reduces virus growthAn international study involving the University of Zurich is also pursuing this approach to flu treatment. The research teams from Switzerland, Germany and the USA analyzed data sets from independent publications on IAV host molecules. These studies focus on the entirety of the genes ("GenOMICs ") and proteins ("ProteOMICs") required for the virus and produce a very large amount of data. Thanks to the comprehensive analysis of these "OMICs" databases, 20 previously unrecognized host molecules that promote the growth of influenza A viruses have been discovered. "These immutable host proteins are essential for virus replication. We can now use them to stop further spread," explains Prof. Silke Stertz from the Institute of Medical Virology at the University of Zurich. One of these host proteins is "UBR4". This protein is required by the virus for the transport of viral proteins to the cell membrane and thus for the construction of new particles. This happens as follows: The influenza A virus enters the host cell and replicates there. The viral components are then brought to the cell surface where they are assembled into new viruses. Up to 20,000 new influenza viruses can emerge from a single infected host cell. The study shows that blocking "UBR4" inhibits the production of new virus particles in infected cells. This made it possible to attenuate IAV replication in mice and thus reduce the course of the disease. The study thus proves that the blocking of host molecules is possible as a therapeutic strategy for treating influenza.Public web portal supports drug developmentThe research team created a Simplified, user-friendly web portal on influenza-host interaction. The site is also accessible to other researchers, allows individual inquiries and offers analysis tools to find host proteins that are likely to play a role in influenza infection. The published data can thus contribute to the development of next-generation influenza drugs. "We anticipate that the approach and use of big data described in this study will bridge the gap between biomedical research and therapeutic development and provide new insights into previously unanswered medical questions," says co-author Sumit Chanda from the Sanford Burnham Prebys Medical Discovery Institute (SBP) in California.