To Stop Rabies, Stop Helping It

If you get rabies and don’t get help in time, you will almost certainly die. While there are a few tantalizing reports of people surviving a case of rabies without medical attention, there are all too many cases of people dying after getting bitten by a rabid animal. The virus sneaks from the bite wound into a nearby nerve and then makes its way through the nervous system. Along the way, it can make people mad and send them into comas before killing them. Officially, over 50,000 people die of rabies each year, but that number is likely a gross underestimate. A lot of rabies cases occur in places where the causes of deaths go unrecorded. In one study in Tanzania, doctors determined that the actual number of deaths from rabies was over 100 times higher than the official count.

The rabies virus is hugely dangerous not only because of its deadliness, but because doctors are so ill-equipped to fight it. The standard way to treat people with rabies is to give them a massive dose of rabies vaccine. The vaccine primes the immune system to fight the rabies virus. On top of the vaccine itself, patients also need to get shots of immunoglobin, a molecule that stimulates the immune system. The treatment leaves a lot to be desired. For one thing, it takes a while for the immune system to rise up against the rabies virus. By the time it has swung into action, the virus may have made too many copies of itself to be wiped out. As a result, getting a rabies vaccine only works if you get to a doctor soon after getting bitten. Making matters worse, the vaccine is expensive and needs to be kept refrigerated. What the world needs is a penicillin for rabies: a pill that’s cheap to make, can sit on a shelf for years, and kill viruses quickly.

In Wired last year, I wrote about one of the teams of scientists who are looking for a rabies antiviral–a group based at a small San Francisco start-up called Prosetta. I paid a visit to Prosetta while researching the story. On the day of my visit, Vishwanath Lingappa, the company’s co-CEO, had a batch of rabies virus protein shells stewing in a flask on his lab bench. I sat in on a meeting where he proudly showed off some of the results of the experiments to his co-workers. Lingappa is an American-born Indian with a deep radio-talk-show-host voice. As he explained the results of his experiment, pointing eagerly to details of his slides, he got more and more excited. Finally, in triumph, he invoked his favorite philosopher, John Dewey, in a bellow: “The givens of experience are not given. They are taken! With great difficulty.”

It would take many more months to get the results ready for publication. Now, finally, Lingappa and his colleagues (including his sister Jaisri, a virologist at the University of Washington, and his daughter Usha) are publishing the study this week in the Proceedings of the Academy of Sciences. They don’t have a cure for rabies yet, but they have found drugs that show a lot of promise. And what makes their study even more interesting is that they took a very unusual path to find those drugs.

Most scientists who look for antivirals hunt for molecules that interfere with a virus’s own molecules. Viruses often make enzymes called proteases, for example, that help prepare new virus proteins. So-called protease inhibitors lock onto the proteases and prevent them from doing their job. These inhibitors have proven effective against HIV and extended the lives of millions of people.

But viruses can’t make new viruses entirely on their own. They need an enormous amount of help from their host cell. The Lingappas have done a number of experiments over the years to figure out the nature of that assistance. They’ve found that many of our own proteins join forces to assemble the pieces of viruses into their final shape.

This figure shows how the Lingappas and their colleagues think the process works. The host cell makes proteins for the virus (A), which begin to stick together (B). But then a swarm of host proteins have to come together around the virus proteins (C ) in order to organize them into their proper shape. This work takes energy, in the form of a molecule called ATP (D). Once the host proteins have finished their work, the new virus is ready to leave the cell (E).

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