Again, after screening many small molecules to see which would best inhibit the PPxY-Nedd4 interaction, the team found two strong candidate molecules. Further testing showed that they could effectively inhibit budding of rabies virus, Marburg VLPs and other PPxY-containing viruses, likely reducing the probability of an infection getting out of control.
"By slowing down virus budding, we may allow an individuals immune system a chance to develop a robust and a protective response," Harty said.
Looking for drugs that target interactions between a virus and host, such as these proteins involved in budding, reduces the likelihood that a virus would mutate to develop resistance, which is an advantage of this strategy, Harty said.
"If they did that, the virus would be compromising its own ability to exit the cell and continue spreading infection," he noted.
This focus on the host side also comes with a potential drawback, the possibility that a drug might compromise the normal function of the protein. Further refinement of the drugs could reduce this possibility, but, when dealing with severe diseases such as Ebola and Argentine hemorrhagic fever, the benefits of treating an otherwise fatal condition would outweigh potential side effects.
These drugs could also be offered in a cocktail with additional compounds that block other stages of the virus life cycle, further amplifying their power. The next steps for these potential antivirals will be to test them in animal models.
"The main reason we're excited is that, if we can come up with something that's effective, it could have a very broad spectrum appeal," Harty said. "That would give us a great way to protect
|Contact: Katherine Unger Baillie|
University of Pennsylvania