In world first, University of Hong Kong scientists develop flu drug using genes from the virus itself
Chinese team file patent in United States after discovering method to ‘cheat’ the virus effective in almost 100 per cent of bird flu cases in mice
A team of Hong Kong scientists on Friday claimed a “vital breakthrough” in the fight against flu by developing a treatment using genes from the virus itself to boost resistance in infected mice.
The discovery could lead to more effective drugs for human patients as new strains of the flu rapidly emerge across the globe, raising the risk of a pandemic.
Researchers from the department of microbiology at the University of Hong Kong’s Li Ka Shing Faculty of Medicine said their “virus against the virus” approach was a world first, and worked through what they termed a double-knockout effect.
It involved isolating the virus’ defective interfering genes and dual-functional proteins, and using them to develop an antiviral drug.
Professor Yuen Kwok-yung, chair of infectious diseases at the department, said the team tested whether a fusion of proteins TAT-P1 and three genes called DIG3 could help laboratory mice with swine flu strain H1N1 2009 or bird flu fight off the illness. H1N1 became a pandemic that year.
The scientists designed the DIG3 genes to inhibit the growth of the flu virus and induce broad anti-flu activity.
They then had to formulate a gene delivery system to introduce DIG3 to the virus cells. This was done using proteins from HIV by fusing TAT and P1 peptides.
The DIG3 genes then exerted their antiviral activity by inhibiting acid production inside the target cells’ endosomes and attacking infected cells.
Laboratory tests showed delivery of the genes to the airway of mice either one to two days before or six hours after infection with a bird flu virus or 2009 H1N1 strain could “reduce body weight loss, improve survival and decrease the amount of flu virus in the lung”.
“It shows that DIG3/TAT-P1 is effective for both prophylaxis and treatment,” the team said.
This method of “cheating” the virus was effective almost 100 per cent of the time in fighting off bird flu in mice, and in 50 per cent of cases against the 2009 H1N1 strain.
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A provisional patent has been filed in the United States and the team’s findings published in the prestigious Nature Communications science journal.
The antiviral treatment could in the future be delivered by a nasal spray like zanamivir, known under the trade name Relenza.
However, the HKU team, which also includes postdoctoral fellow Dr Zhao Hanjun and clinical associate professor Dr Kelvin To Kai-wang, would need about HK$100 million (US$12.74 million) to develop the drug and market it.
Zhao said their technique had “important implications for the future treatment of flu” as well as other viral infections such as Middle East respiratory syndrome and severe acute respiratory syndrome.
“This is the first time defective interfering genes have been shown to protect flu-virus-infected mice,” he said, and the “first gene delivery system with antiviral activity against the flu virus”.
Yuen told the Post he was confident investors in mainland China would be interested in the treatment as there was a great deal of money being spent on drug development across the border.
“The important thing is to get things done,” he said. “Another pandemic could come so easily ... because the population is growing, the number of pigs and chickens is growing ... It might not be longer than 30 years.”
With large swathes of the world population potentially lacking immunity to any new flu strain, an outbreak could spark a pandemic similar to the Spanish flu (H1N1) of 1918, Asian flu (H2N2) in 1957, Hong Kong flu (H3N2) of 1968 or Mexican flu (H1N1) seen in 2009.