H7N9 Influenza Therapeutics: 6 Proven Drug Targets Discovered Through Immune Research
H7N9 influenza therapeutics research has taken a significant step forward with a study published ahead of print in the Journal of Virology, identifying six FDA approved drugs that could potentially be repurposed to treat this highly virulent strain of avian influenza. The research, led by Juliet Morrison of the University of Washington, Seattle, takes a novel approach to fighting severe flu by targeting the host immune response rather than the virus itself.
A New Approach to Treating Severe Influenza
The conventional approach to influenza treatment focuses on attacking the virus directly. However, Morrison and her collaborators argue that the severity of influenza disease often results more from the strength of the immune response than from the virus alone. Turning down that overactive immune response, rather than targeting the pathogen itself, may be a more effective strategy for reducing the severity of disease caused by highly virulent strains like H7N9.
“We set out to characterize the response to the severe disease causing H7N9 virus and compare it to responses elicited by other serious flu viruses in a mouse model of infection,” said Morrison. That work centered on determining which genes are activated during H7N9 infection and how those activation patterns differ from milder influenza strains.
Gene Expression Signatures Distinguish Severe Influenza
One of the core findings driving the H7N9 influenza therapeutics discovery is that highly virulent flu viruses produce distinct gene expression signatures compared to less severe strains. Michael Katze, a University of Washington colleague and co author in whose laboratory the work was performed, explained the significance of this finding.
“We have found that viruses that cause severe illness, like H7N9 and the infamous 1918 virus, trigger gene expression signatures that are different from the signatures seen in milder infections,” said Katze. “Importantly, we can exploit these signatures for antiviral drug discovery.”
The data indicates that severe influenza strains are associated with increased transcription of inflammatory cytokine genes and reduced transcription of lipid metabolism and coagulation genes. These patterns point to specific biological pathways that can be targeted therapeutically to modulate the harmful immune response without directly attacking the virus.
How the 6 H7N9 Influenza Therapeutics Were Identified
The research team used a computational biology approach to identify the six potential H7N9 influenza therapeutics. Investigators searched databases containing gene expression profiles of cultured human cells treated with a wide range of drugs. The goal was to identify drugs that produced gene expression patterns that were essentially the reverse of those induced by the H7N9 flu virus. Drugs producing this opposite signature could potentially counteract the harmful host immune response triggered by the virus.
“Six of these drugs are FDA approved and could potentially be repurposed as H7N9 influenza therapeutics,” said Morrison. “I believe that computational biology represents an exciting new way to study viruses and to discover drugs to fight them.”
This repurposing approach is particularly valuable because FDA approved drugs have already passed safety evaluations, potentially accelerating the path from discovery to clinical use. Investigators from the Centers for Disease Control and Prevention and the United States Department of Agriculture also participated in this research, underscoring its public health significance.
Why H7N9 Demands Serious Scientific Attention
The H7N9 avian influenza strain, which emerged in February 2013, caused those infected to become extremely ill in ways reminiscent of the 1918 influenza pandemic, the deadliest on record. The clinical severity, high hospitalization rates, and limited treatment options at the time of its emergence highlighted the urgent need for novel H7N9 influenza therapeutics capable of addressing the biological mechanisms driving disease severity.
Further study of the gene expression phenomena identified in this research is expected to deepen the understanding of severe influenza and help investigators identify additional therapeutic candidates. The computational approach used here may also prove applicable to other highly virulent respiratory viruses, expanding its potential impact beyond H7N9.
Clinical Research in Infectious Disease at FOMAT
At FOMAT, we actively support clinical research in infectious disease and antiviral development across the United States. Research like this, originally published by the American Society for Microbiology, illustrates why continued investment in computational biology and clinical trials for infectious disease therapeutics is essential for public health preparedness.
Visit our Active Studies page to explore current infectious disease research opportunities at FOMAT.
Source: American Society for Microbiology, July 21, 2014