It may sound like a blockbuster movie crossover, but researchers are investigating whether so-called matrix proteins could prevent the sort of global pandemic depicted in the film "Contagion." The proteins are central to a new a stage in the formation of paramyxoviruses—a finding that could help create future therapies combat the potential pandemic-causing pathogens.
Effective therapies are still needed for certain paramyxoviruses—a family of viruses that includes measles, Nipah virus and mumps, as well as Newcastle disease in birds and canine distemper for dogs.
"Just imagine if a paramyxovirus emerged that was as contagious as measles and as deadly as Nipah," Michael Norris, Ph.D., assistant professor at the University of Toronto, said in a July 20 release. The idea is actually the basis of 2011 thriller "Contagion," in which a fictional paramyxovirus triggers a disastrous pandemic.
Now, Norris and an international team of scientists have detected a life cycle stage of measles and Nipah viruses that could inform future drug discovery efforts. Their findings, published in Science Advances, identify the trigger that starts the irreversible formation process of virus assembly.
At a Purdue University lab, the researchers used imaging techniques such as X-ray crystallography and electron microscopy to understand the viral assembly process. Special virus proteins, dubbed matrix proteins, drive development, forming a lattice against the cell membrane and guiding other proteins to form a new virus.
The lattice then pushes the membrane out, creating a “bud” that recruits other viral proteins and then splits away to form a new virus that can infect a different host cell.
The scientists found Nipah virus matrix proteins actually change their structure to open a binding pocket for a particular lipid molecule. The pocket doesn’t exist before membrane binding, and its existence can be used as a new target for stopping the assembly process, they said.
While Nipah virus and measles have different genomes, their matrix proteins appear almost identical, according to Norris. Further studies are still needed to better understand how matrix proteins recruit and interact with the other viral proteins during assembly, but the discovery is a good jumping off point.
Due to the similarities between this family of viruses, the researchers hope to design a pan-paramyxovirus therapy that could interrupt the viral assembly process. They pointed to Gilead Sciences' phase 3 drug lenacapavir—which is designed to interrupt the assembly process of HIV—as validation of this approach.
"This HIV therapy is a proof of principle that targeting viral assembly is a viable strategy for drug development," Norris added.