There is only one good way to fight most viruses: get vaccinated before you catch them. Once you have a virus there are very few drugs to fight it the way antibiotics fight bacteria. A new drug promises to do just that, though – to measles.
It’s not a moment too soon. Epidemiologists have dreamed of eradicating measles. But even though the vaccine works very well, cases of measles are increasing in rich countries because parents refuse to vaccinate their children owing to inaccurate claims that vaccines cause harm.
Moreover, this week saw the first-ever report that a vaccinated person can spread the measles virus. Public health officials in New York City, who found the case, speculate that it may have happened because the battle against measles has been so effective. People who are immune to measles because of vaccination, not disease, can need periodic boosters to remain immune. When measles was common, exposure to cases acted as a booster – but now, measles is relatively rare.
A measles anti-viral drug could help counter both problems, by stopping the virus from spreading far in outbreaks – either among the unvaccinated, or when the vaccine has failed.
Just such a drug may now be within reach. It has the unmemorable name of ERDRP-0519, and was discovered in 2007 by Richard Plemper of Emory University in Atlanta, Georgia, and his colleagues. His team screened 34,000 compounds for anti-measles activity, using an automated system in which cultured cells with replicating virus glowed. Because viruses are not alive, anti-viral drugs do not aim to kill, just to stop replication.
ERDRP-0519 did that by blocking measles’s RNA polymerase, an enzyme vital for replication. The next step was testing it against a real infection. Because only primates get measles, the researchers tried it first against a similar virus, canine distemper, which is lethal in ferrets.
The ferrets were dosed orally for two weeks, either starting a day before, or three days after they were infected with distemper. Ferrets that didn’t get the drug died. Ferrets that got the drug at three days, however, lived – and even developed enough immunity to the virus that they were completely protected when infected a second time.
But ferrets that got the drug just before they got the virus died of distemper two weeks after stopping the drug, and never developed immunity. Tests of their immune reactions suggest that the drug stopped the virus replicating so completely that the ferrets never developed immunity to it.
Consequently, they were vulnerable to remaining virus that resurged once treatment stopped.
So to work in humans, the drug will have to be given after someone has been exposed, but before the onset of symptoms. This can take two weeks, so there should be time to treat all the social contacts of someone who has developed measles. After symptoms start, says Plemper, the measles virus has stopped replicating anyway, so blocking further replication will have little effect.
“We will next test experimentally how late after infection treatment can be initiated,” says Plemper. They will also test it against real measles in squirrel monkeys. Plemper hopes giving the drug before infection will be more helpful in measles than distemper, because measles is a milder disease and just weakening it a bit might be good enough.
Another potential problem with a measles anti-viral drug is that it might lead to the development of mutant measles viruses that can resist the drug, much as bacteria can become resistant to antibiotics. The nightmare scenario would be if these mutants happened to be more virulent than measles, which although it is the most contagious human virus known, is not often lethal. Giving birth to a nastier measles virus could be worse than never using the drug at all.
So the team tested the drug against measles virus in culture, and found it did indeed engender resistant mutants – but they were all less transmissible or virulent than natural measles. That might not be enough to ease health workers’ fears, though: flu mutants resistant to the anti-viral drug Tamiflu seemed equally unthreatening in similar lab tests – until 2007, when a resistant mutant completely dominated one strain of flu.
Any use of the drug would have to be accompanied by strict monitoring for resistant strains, says Plemper, but it is encouraging that all the points where genes mutated to produce drug resistance normally do not mutate in wild measles viruses, suggesting the virus needs them to remain unchanged.
Another potential issue is that the availability of an anti-viral drug might further encourage people to reject vaccination, by making measles seem less threatening. This defeats the whole point, says Plemper. “Possible measles eradication must by driven by vaccination,” he says. “We developed this drug to rapidly suppress local outbreaks in populations with good vaccination coverage.”
That way, the drug can act in synergy with the vaccine, plugging gaps in vaccination coverage and giving more hope of one day eradicating measles. “Combined, they may one day succeed in eradicating measles totally,” he says.
Journal reference: Science Translational Medicine, DOI: 10.1126/scitranslmed.3008517