As it turns out, one of these pieces, a protein called VP4 that helps the virus attach to the cell, is very similar across nearly all rhinoviruses. It had been overlooked because it was exposed only sometimes on the outside of the capsid.
Preliminary research in cell cultures done by Smith’s team in 2009 demonstrated that a VP4-type vaccine conferred immunity to three strains of rhinoviruses, suggesting that a vaccine of that kind might be useful for protecting against many colds. But the prospect is far from a sure thing. “I’m not going to oversell it,” Smith remarks. It turns out that VP4 is not normally prominent enough to provoke a serious response. To use a protein like VP4 in a vaccine, he says, you would have to somehow convince the immune system to go after it.
An idea put forth two years ago by Gregory Tobin of Biological Mimetics in Frederick, Md., may offer a way around this difficulty. Tobin and his colleagues suggested that delivering large amounts of a protein not normally recognized by the immune system might evoke a protective immune response. This strategy has shown some encouraging signs in early work with foot-and-mouth disease and is being investigated for HIV, but the strategy is not yet proven.
As for drugs that might act once a cold sets in, the pitfalls of pleconaril still await. “The infection won’t kill you, so the treatment has to be safe as water,” Smith says. Ronald B. Turner, a cold virus researcher at University of Virginia, echoes that thought: “It has to be very effective, it has to be absolutely cheap, and it has to be completely safe.” The bar is thus set very high. Even after more than 50 years of work on the rhinovirus, not a single drug that targets it is on the market.
Although few drug companies are working on the common cold anymore, some are still taking aim at rhinoviruses. Over the past few decades research has implicated the viruses in serious complications of asthma, emphysema and cystic fibrosis. “From a drug discovery perspective, if you have efficacy for a more severe illness, the risk that your drug is going to wash out based on toxicity, safety and cost issues becomes less,” Turner says.
Targeting closely related groups of rhinoviruses offers one direction for treatment. In 2009 Stephen B. Liggett of the University of Maryland and his colleagues published the complete genomes of 109 rhinoviruses, including an evolutionary tree depicting their relationships. “If you could look at that tree and draw a circle around a group of viruses that cause a really powerful exacerbation of asthma, you could target those [viruses] directly,” Liggett says. And closely related viruses might respond more consistently to a treatment than hundreds of more diverse viruses do.
In the end, it may not be the worst thing that rhinoviruses have so cleverly evaded our grasp. Some research suggests that colds may provide temporary immunity to more severe infections. For example, the 2009 pandemic H1N1 flu did not spread in earnest in France until after the cold season was over. Jean-Sebastien Casalegno of the French National Influenza Center reports that colds among children appeared to reduce the likelihood of infection with H1N1, although he emphasizes that the connection is still just a hypothesis. “If we completely succeed in eliminating all rhinovirus infections, other respiratory viruses, such as influenza, may move into that niche,” he speculates.
It is possible that virus-fighting cold treatments in the future would not eliminate infection but might still make you feel better. Turner points out that a third of all rhinovirus infections do not produce cold symptoms. “Clearly, the inflammatory response isn’t necessary for elimination of the virus, because those people get over their infections just like everybody else,” he says. To that end, future treatments might tamp down the immune response or reduce the amount of virus in the body just enough to elude symptoms. But as with all the potential cold cures, there is a caveat—would we want to impede our immune systems? In so doing, we might trade a minor nuisance for ailments or side effects that are even more severe. That, unfortunately, is the inescapable, central conundrum of curing the cold: the cure may be worse than the inconvenience.
This article was originally published with the title Curing the Common Cold.