Big data unlocks new targets to treat influenza

A team of scientists have tapped into publically available large-scale ‘Omics’ databases to identify new targets to treat influenza.

The study reflects a breakthrough approach using advanced computational designs to identify new factors that can be targeted to prevent viruses from spreading. The research team also created an open access website for scientists to cull additional host-targets to develop the next-generation of anti-influenza drugs.

“Traditionally, physicians have treated the flu with drugs that directly block the influenza virus,” said Sumit Chanda, Ph.D., director of the Immunity and Pathogenesis Programme at Sanford Burnham Prebys Medical Discovery Institute (SBP). “Although these drugs have been helpful, many patients fail to respond because viruses, especially influenza A virus (IAV), can mutate, rendering them resistant to available drugs. Our research efforts are focused on finding unalterable host molecules – the ones within our bodies – that viruses hijack to spread and create full blown infections.”

By integrating multiple IAV host-pathogen ‘Omics’ databases, including one generated by the work in this study, the research team identified 20 previously unrecognised host proteins required for IAV replication. One protein, UBR4, was singled out as a pivotal host protein that the virus uses to bud off from the host cell membrane and form spherical vesicles that transmit the virus within and between individuals.

The study showed that blocking UBR4 in vitro and in vivo reduced IAV replication and pathogenesis, establishing proof-of-concept of the strategy to target UBR4 as an influenza treatment.

Big data no longer ‘merely a catchphrase’

“Our work illustrates how the computational analysis of large datasets from multiple independent studies can reveal novel host factors and networks involved in virus replication as potential targets for therapeutic intervention,” said Adolfo Garcia-Sastre, Ph.D., director of the Global Health and Emerging Pathogens Institute at the Icahn School of Medicine at Mount Sinai. “‘Big data’ is no longer merely a catchphrase – it is a real tool to help scientists address the world’s most serious public health threats.”

The research team has created a simplified, user-friendly web portal of the integrated data that reflects the biochemical landscape of essential influenza-host interactions. The site enables customised queries and analysis tools to find host proteins likely to play a role in influenza infection.

“We anticipate that the approach described in this study, which is packaged as an accessible web interface, will provide a bridge for those on the frontlines of biomedical discovery and therapeutic development to leverage ‘big data’ and achieve transformative treatments for unmet medical needs,” Chanda concluded.