Scientists at Imperial College London, in collaboration with Public Health England, have discovered that two genetic mutations would be needed for the virus to develop resistance to favipiravir, an experimental antiviral developed in Japan.
Favipiravir is not currently licensed in the UK for the treatment of flu but has shown to be effective in clinical trials to date and has the potential to be used in the event of a flu pandemic where other drugs, such as Tamiflu, might fail.
The researchers caution that the influenza virus has only so far been shown to develop resistance to the drug in laboratory studies, and it is unclear if the same would happen in a pandemic. However, their findings highlight a mechanism by which influenza and other viruses could potentially overcome such drugs used in the event of an outbreak and so should be closely monitored.
It was previously thought that the influenza virus was unable to overcome favipiravir, with laboratory, animal and clinical studies showing little evidence of resistance. However, the latest findings, published this week in the journal PNAS, are the first to show that influenza could develop resistance to the drug.
Professor Wendy Barclay, from the Department of Medicine and Action Medical Research Chair in Virology at Imperial, who led the research, said: “We’re alerting the world to the fact that RNA viruses, like influenza, can readily adapt to their environment and evolve, and that while favipiravir could be a potentially important drug in a pandemic situation, resistance can emerge.”
Favipiravir acts by targeting an enzyme called RNA polymerase used by influenza to copy its genetic material. Clinical trials have shown the drug to be effective in treating flu in humans and it has also been tested against other RNA viruses, like ebola and chikungunya, which rely on the same type of enzyme to replicate, showing promise in pre-clinical trials.
More information: Daniel H. Goldhill et al, The mechanism of resistance to favipiravir in influenza, Proceedings of the National Academy of Sciences (2018). DOI: 10.1073/pnas.1811345115