We might be inching closer to a holy grail of medicine: an incredibly effective flu-killing drug that the virus can’t quickly adapt to. A new experimental treatment was able to rapidly reduce the flu virus in ferrets, but human trials are still a ways off.
Researchers at Georgia State and Emory University have spent the last few years trying to develop what they’ve billed as next-generation antivirals. One lead they’ve followed is a molecule that can attack and inhibit a wide variety of RNA viruses — including chikungunya, Zika, and influenza — called N4-hydroxycytidine (NHC). In animal experiments, at least, NHC seems to throw a big wrench into how an RNA virus replicates itself, leading to disastrous, fatal mutations.
A study with non-human primates, however, suggested that NHC wouldn’t easily be absorbed by the human body, limiting its potential effectiveness. So the researchers created different experimental drug candidates based on NHC that seem to get over this hurdle. And it’s one of these candidates, called EIDD-2801, that was tested out in ferrets for the new study, published Wednesday in Science Translational Medicine.
As luck would have it, ferrets are remarkably similar to people in how their bodies are attacked by the influenza viruses that infect us, making them an ideal animal model for flu research. For the researchers’ experiments, the ferrets were first infected with different types of flu — the kinds that cause us seasonal sniffles as well as the strain of flu behind a 2009 pandemic — then they were treated with varying oral doses of EIDD-2801 a day into exposure.
They found that EIDD-2801 was able to dramatically reduce the viral load of these flu strains “by multiple orders of magnitude” within a day’s time, along with alleviating fever and other symptoms of infection — with its performance being comparable to or better than an existing antiviral used to treat flu. And when EIDD-2801 was given to the ferrets immediately before and after flu exposure, it prevented illness from showing up at all. Experiments involving human lung tissue created in a petri dish found similar evidence of EIDD-2801’s lethality.
“The compound is highly efficacious against influenza,” senior study author Richard Plemper, a professor at Georgia State’s Institute for Biomedical Sciences, said in a release from the university. “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.”
RNA viruses are more genetically unstable than viruses that replicate using DNA. But this instability comes with a benefit, because they can quickly mutate into versions that resist the drugs and vaccines we would want to use on them. That’s why we need a new vaccine every year for seasonal flu, and it’s also why some current antivirals developed against the flu are already practically useless.
But when Plemper and his team sequenced the genomes of influenza viruses exposed to sublethal doses of EIDD-2801, they found no evidence of any beneficial mutations that might grant them resistance. That finding doesn’t mean the virus couldn’t become resistant to EIDD-2801 someday, but it does suggest it won’t be easy.
Still, as useful as ferrets are for studying flu, the real test of EIDD-2801 will have to come in clinical trials involving humans. Plemper and his co-authors say that such trials may get underway by next year.