Discoveries in a key early life cycle stage of the Paramyxoviruses (e.g. Measles)

Good news! Targeting the viral assembly of a new virus in host cell before it exits host cell to infect other cells has great potential for designing new effective treatments!

"Paramyxoviruses have the potential to trigger a devastating pandemic. This family of viruses includes measles, Nipah virus, mumps, Newcastle disease and canine distemper.

“The infectiousness of measles is unmatched by any known virus. If one person with measles coughs in a room with 100 unvaccinated people, around 90 would become infected,” ... “Nipah virus is not as contagious, but it is incredibly lethal, with between 40 percent and 90 percent of infections causing death.”

“Just imagine if a paramyxovirus emerged that was as contagious as measles and as deadly as Nipah,” ...
published the first-ever look at a key stage in the life cycles of measles and Nipah viruses.  ...
During viral assembly, key proteins and genetic material rush to specific areas on infected host cell membranes. Special virus proteins, called “matrix” proteins, come together to form a lattice against the inside of the cell membrane. Matrix proteins are the drivers of the virus assembly process. ... “field marshals” that gather and guide the other proteins needed to form a new virus. Matrix proteins also give a virus its shape. ...

As viral assembly continues, the lattice of matrix proteins begins to push the membrane outward to form a “bud” and recruits other viral proteins to this site. Once the bud has all the needed components in place, it splits away from the parent cell to form a new virus that can then infect a new host cell.

Researchers hope by understanding viral assembly better, they can design therapies that interrupt the process. This approach holds promise; the drug Lenacapavir targets the assembly process of HIV and is in clinical trials right now, and Norris says there’s potential to use the same strategy to stop paramyxoviruses. “This HIV therapy is a proof of principle that targeting viral assembly is a viable strategy for drug development,” ...

Then came a big structural surprise. The team found that Nipah virus matrix proteins actually change their structure to open up a lipid-binding pocket for PI(4,5)P2. ... 

that this pocket doesn’t exist prior to membrane binding—and the pocket would not have been spotted without the structure captured in this study. The discovery of this pocket revealed a brand-new target for developing inhibitors of the assembly process. ...
A broad paramyxovirus therapy could also protect livestock from disease and ensure food security. ..."

From the abstract:

"Measles virus, Nipah virus, and multiple other paramyxoviruses cause disease outbreaks in humans and animals worldwide. The paramyxovirus matrix (M) protein mediates virion assembly and budding from host cell membranes. M is thus a key target for antivirals, but few high-resolution structures of paramyxovirus M are available, and we lack the clear understanding of how viral M proteins interact with membrane lipids to mediate viral assembly and egress that is needed to guide antiviral design. Here, we reveal that M proteins associate with phosphatidylserine and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] at the plasma membrane. Using x-ray crystallography, electron microscopy, and molecular dynamics, we demonstrate that PI(4,5)P2 binding induces conformational and electrostatic changes in the M protein surface that trigger membrane deformation, matrix layer polymerization, and virion assembly."

» Putting the brakes on “budding” viruses New measles, Nipah research offers a window into viral assembly

Measles and Nipah virus assembly: Specific lipid binding drives matrix polymerization (open access)

This image shows how viral proteins gather inside a cell membrane to form a sort of bubble before “budding” off to spread infection.

Fig. 8. Matrix proteins self-assemble in the presence of PI(4,5)P2 and form spherical and filamentous extensions from cells.