Nipah virus: a doctor explains the signs and symptoms
Paramyxoviruses are a family of negative-strand RNA viruses whose members include measles, Nipah virus, mumps, Newcastle disease, and canine distemper. Biochemist Professor Michael Norris from the University of Toronto said: ‘The infectivity of measles is unmatched by any known virus. “If a person with measles coughs in a room with 100 unvaccinated people, around 90 would be infected.”
Teacher. Norris continued: “The Nipah virus is not as contagious, but it is incredibly deadly, with between 40% and 90% of infections causing death.
“Just imagine if a paramyxovirus emerged that was as contagious as measles and as deadly as Nipah.”
(And for those lacking in imagination but fond of big-screen medical thrillers, that dire hypothesis plays out in the 2011 film “Contagion,” which claimed 26 million lives worldwide before the protagonists managed to develop a effective vaccine against imaginary paramyxovirus.)
Pictured – a child with measles, a highly contagious paramyxovirus
Pictured: A giant multinucleated cell caused by measurements
Back in the real world, however, Prof. Norris and his international team of colleagues have ideas for how we might stop a real paramyxovirus pandemic in its tracks.
Specifically, the team published the first-ever study of a key stage in the measles and Nipah virus life cycles.
The paper’s co-author and structural biologist, Professor Erica Ollmann Saphire of the La Jolla Institute of Immunology, explained, “This work solves a long-standing mystery: how viruses fit together.
“We know that the many pieces of a virus come together at the cell membrane, but we didn’t know what the trigger was that starts this irreversible assembly process.”
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According to Prof. Norris, 40-90% of Nipah virus infections cause death
Pictured: Viral proteins congregate inside a cell membrane before ‘budding’ to spread infection
In their study, the researchers used various imaging techniques – including X-ray crystallography and electron microscopy – to capture how the measles and Nipah viruses fit together.
This process, they explained, sees key proteins and genetic material rush to specific areas on the membranes of infected host cells.
They are driven by special viral “matrix” proteins that come together to form a network against the inside of the cell membrane – binding to a lipid molecule in the membrane to provide meeting points for virus assembly.
Matrix proteins change shape to create a pocket for lipid binding, a movement that also causes them to adopt a shape that encourages network assembly.
These “field marshals” – like prof. Norris likes to call them – then gather, guide and shape the other proteins needed to produce a new virus.
The matrix protein network pushes the cell membrane outward, forming a “bud” that recruits other viral proteins to the site.
Once the bud has all of its required components in place, it separates from its host cell and moves on to infect a new one.
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Newcastle disease is a paramyxovirus that affects birds and is known to wipe out entire flocks
Co-author and Professor Robert Stahelin of Purdue University added: “This study succeeds in identifying how paramyxoviruses are able to utilize a host cell lipid for virus propagation.”
The team hopes that if we can better understand how paramyxoviruses assemble, then we can design therapies that interrupt the process.
This approach is not unprecedented — a drug called Lenacapavir that is currently in clinical trials uses the same principle to target the HIV assembly process.
Teacher. Norris said, “This HIV therapy is proof of principle that targeting viral assembly is a viable strategy for drug development.”
Teacher. Stahelin agreed, adding, “This work will inform future drug discovery efforts.”
Such drugs could work, for example, by blocking the lipid-binding pocket that matrix proteins use to latch onto cell membranes.
While different paramyxoviruses like measles and Nipah have wildly different genomes, the beauty of the researchers’ approach is that they use matrix proteins that are virtually identical in appearance.
Teacher. Norris explained, “Because these matrix protein structures are highly conserved, we could potentially target one virus and have an inhibitor that could target all other viruses in that family.”
Broad paramyxovirus therapy could have many applications – from tackling measles outbreaks around the world and tackling the annual outbreaks of Nipah seen in Bangladesh and India to helping protect livestock from disease, thereby boosting the Food Safety.
Newcastle disease, for example, is a paramyxovirus that affects birds and has been known to wipe out entire flocks. Between 2018 and 2020, an outbreak among poultry in California forced the culling of a shocking 1.2 million birds.
Teacher. Norris and his colleagues have already begun the search for suitable matrix protein inhibitors – and have narrowed a list of 7.4 million potential drug candidates down to 100 that will now undergo further testing.
The full results of the study have been published in the journal Science Advances.
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