Ebola Virus
Ebola is one of the deadliest viruses humans encounter — roughly half of those infected die, and in the worst outbreaks, nearly nine in ten.
The disease
Ebola virus disease is a hemorrhagic fever caused by four related filoviruses: Zaire, Sudan, Bundibugyo, and Taï Forest. After a 2–21-day incubation, symptoms begin like the flu — fever, sore throat, muscle pain — then escalate to vomiting, diarrhea, and in some patients, internal and external bleeding. Death typically follows one to two weeks after symptoms begin, most often from shock caused by massive fluid loss.
The virus moves between people through direct contact with body fluids. Fruit bats are the suspected natural reservoir; outbreaks usually begin when humans contact an infected animal, often during the hunting or handling of bushmeat. The first recorded outbreaks, in 1976, hit Sudan and Zaire — the latter now the Democratic Republic of the Congo. The largest epidemic, in West Africa from 2013 to 2016, infected over 28,000 people and killed more than 11,000. The 2018–2020 outbreak in eastern DRC was the second-largest in history.
What we have to fight it
The picture has improved dramatically in recent years. The rVSV-ZEBOV vaccine (Ervebo) was approved in the United States in 2019 and prevents Zaire ebolavirus infection. Two antibody therapies — Inmazeb, a three-antibody cocktail, and Ebanga, a single antibody — were approved in 2020 to treat active Zaire infections, both substantially reducing mortality. But no approved vaccine or treatment yet covers Sudan ebolavirus or the other less-common species.
VP35 and a hidden door
One of the most important Ebola proteins is VP35. It helps the virus stay invisible to the immune system long enough for the infection to take hold. Static experimental structures of VP35 made it look untargetable — a smooth surface with no obvious pocket where a drug could grip on. So Folding@home's Bowman lab simulated VP35's motion and uncovered something the snapshots had missed: a transient, "cryptic" pocket that opens and closes as the protein moves.
In a 2024 paper, Mallimadugula and colleagues showed that this cryptic pocket isn't just a quirk of motion — it has a function. When the pocket is open, VP35 binds the viral genome's RNA more tightly than it does in the closed conformation. Because the pocket matters to the virus, a drug that locks it shut would be hard for the virus to evolve resistance against — the same mutations that closed the pocket would impair the virus itself.
Work on VP35 and related filovirus proteins continues, including a 2025 paper extending the cryptic-pocket approach across the broader filovirus family. An earlier 2018 study analyzed how Ebola's nucleoprotein assembles into the long helical structures that wrap the viral genome.