Successful animal experiments of an antiviral drug which induces mutations in the genetic material of influenza virus, could be a “groundbreaking advance in influenza therapy”, according to the team which carried out the study at the Institute for Biomedical Sciences at Georgia State University.
The drug, which can be taken orally, works by blocking RNA polymerase, the enzyme that plays a central role in replicating the genome of influenza virus, causing mutations in the viral genome.
If enough mutations occur, the genome becomes nonfunctional and the virus cannot replicate.
“The compound is highly efficacious against influenza,” said Dr Richard Plemper, senior author of the study and a professor in the Institute for Biomedical Sciences.
“It’s orally available, it’s broad spectrum against all influenza virus strains tested, and most important it establishes a high barrier against viral escape from inhibition.”
Influenza, caused by a contagious respiratory virus, is characterised by fever, cough, headache, muscle and joint pain, severe malaise, sore throat and sometimes gastrointestinal symptoms.
Patients in higher risk groups, such as older adults and individuals with compromised immune systems, frequently require hospitalisation.
Each year, seasonal influenza results in 30,000 to 80,000 fatalities in the US. In the UK around 10,000 may die from flu each year, with the elderly most at risk. Around 13,000 people died in Britain from the illness in 2008-09. Around the world about half a million deaths are attributed to flu each year.
The seasonal flu vaccine is only moderately effective, and licensed antivirals are compromised by rapidly emerging viral resistance to the drugs.
In the study, the new antiviral drug was tested in ferrets, the most informative animal model for human influenza disease, against various strains that include seasonal and pandemic viruses, such as the swine-origin influenza virus responsible for the 2009 pandemic.
The researchers found the antiviral drug efficiently inhibited replication of all of these strains.
Virus burden (the quantity of virus in a given volume) dropped rapidly after treatment, and the duration of fever was significantly shorter in treated ferrets than in control animals which did not receive the drug.
“We think that the next generation of influenza antiviral drugs must not only be efficacious and safe, but also address the resistance problem,” said Dr Mart Toots, first author of the study and a research assistant professor at the Institute for Biomedical Sciences.
Dr Plemper added: “We have not identified specific resistance mutations yet and are confident to say that the genetic barrier against viral resistance is high.
“We believe that this compound has high clinical potential as a next-generation influenza drug that combines key antiviral features.”
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