Have you been following the news out of West Africa? The spread of the Ebola virus there is truly heartbreaking. While residents of the U.S. have little to fear from Ebola (unless you’re planning to travel to that part of the world), researchers here are still working hard to come up with new, potential therapies. You might be surprised to hear, however, that some of the most ground-breaking work is being done at the University of Pennsylvania’s veterinary school.
Dr. Ronald Harty is an associate professor of microbiology at Penn Vet, and in conjunction with other scientists from Penn Vet, the U.S. Army Medical Research Institute of Infectious Disease, Thomas Jefferson University, and Fox Chase Chemical Diversity Center, he is developing potential drugs that could revolutionize the way that Ebola and other viruses affecting people and animals are treated.
I recently talked to Dr. Harty to learn more about his work. When asked why research into Ebola was being undertaken at a veterinary school, he replied:
"I’m not a veterinarian, but I’m here at the vet school doing basic research working primarily on Ebola and other hemorrhagic fevers. But, we also do a lot of work on vesicular stomatitis virus (VSV) and rabies virus [both of which are significant animal pathogens]. VSV is actually a sort of distant cousin to Ebola. The makeup of the viruses — how they bud [exit the cell] and replicate, their genomes, the proteins they make — are very similar. VSV has served as a wonderful model system. It’s a virus we can fairly easily work with, using it as a surrogate to understand budding in the more pathogenic Ebola virus."
One of the big problems in developing anti-viral drugs, particularly those that are useful against RNA viruses like Ebola, VSV, rabies, influenza, West Nile virus, human immunodeficiency virus (HIV), feline immunodeficiency virus (FIV), and feline leukemia virus (FELV), is that when these organisms replicate, they can mutate very rapidly and develop resistance to drugs. Dr. Harty explained that his team’s approach is innovative in that they are trying to develop drugs that are “host oriented.”
"We are trying to target a virus-host interaction with our compounds. What we and others have found is that viruses like Ebola, rabies, and VSV hijack or recruit host proteins that help the virus to bud. The virus actually steals the function of these host proteins and uses it for its own purpose. We hypothesize that if we can target that virus-host interaction, we can block or slow down budding. We predict that the virus would not be able to mutate as readily to get around an inhibitor that is targeting, at least in part, a host function in comparison to one that just targets a specific viral protein.
"The step that we are targeting is the very last step in budding, so the viruses are on the surface of the host cell. They can’t quite break free but are where the immune system can react to that pathogen.
"[Budding] is analogous to having a car thief trying to speed away from a robbery. The drug would act like spike strips put down in front of that car; it would slow the infection down. We hope that will allow the immune system more time to develop a response, like the spike strips allow the police officer to catch up to the thief and arrest him.
"The other really exciting part of the development of these compounds is they potentially have a very broad spectrum range of activity because many of these RNA viruses bud from cells using a similar mechanism. They all hijack the same host pathways. So what we and others have found is that if we can block budding of Ebola virus, for example, that same compound can block budding of other viruses like rabies, VSV, Marburg virus or even HIV. There is the potential to have a drug that could be effective against many different families of RNA viruses."
Dr. Harty’s work reveals the deep connections between animal and human health. Hopefully, the compounds he and his team are developing eventually will benefit us all.
Dr. Jennifer Coates