Remember ebola?

Kyoto, Japan -- Six years before the start of the COVID-19 pandemic, an Ebola outbreak in West Africa had people fearing the possibility of a global outbreak. This was the first time many had ever heard of the virus, but since it was first identified in 1976, there have actually been more than 20 serious Ebola incidents. Thankfully, none of them had the global reach of the coronavirus.

Ebola has not been eradicated, however. This deadly virus, which causes severe hemorrhagic fever in humans and has a fatality rate of about 50%, is still at large and could thus still cause a major outbreak, unless further research finds an effective solution.

A major challenge lies in the virus' structure and regulatory mechanisms, which have remained largely unclear. In particular, scientists have long struggled to fully understand its nucleocapsid, the protein shell that plays an important role in genome replication and transcription.

This motivated a team of researchers at Kyoto University to capture the first high-resolution structure of the detailed nucleocapsid using single-particle cryo-electron microscopy, visualizing molecular structures at near-atomic resolution by rapidly freezing study samples.

"Using cryo-electron microscopy, we were able to view the nucleocapsid structure at 4.6 angstrom resolution for the first time," says corresponding author Takeshi Noda. One angstrom, or Å, is equal to one hundred-millionth of a centimeter.

This visualization allowed the researchers to observe the sophisticated interactions between the nucleocapsid's structural components, particularly between NP, a nucleoprotein, and VP24, a viral protein. Both are essential for nucleocapsid assembly, the regulation of RNA synthesis, and intracellular transport.

When observing the spiral shape of the NP-RNA complex at the center of the nucleocapsid, the researchers noticed an unexpected pattern with two VP24 molecules binding to two NP molecules in different arrangements.

Subsequent analysis revealed the specific molecular interactions that govern these processes. Notably, VP24 plays a dual role: while one VP24 interacts with an NP molecule to inhibit viral RNA synthesis, another attaches to an adjacent NP to regulate nucleocapsid assembly and transport, demonstrating how the nucleocapsid can dynamically switch between genome replication and virion packaging.

"Our first high-resolution structure of the Ebola virus nucleocapsid provides detailed insights into the interactions within the nucleocapsid complex," continues Noda, "unveiling the relationship between molecular interactions and functional regulation."

These insights are crucial for the development of targeted antiviral therapies, which could focus on disrupting the assembly or functions of the nucleocapsid. Furthermore, with continued effort and collaboration, these findings may contribute to improving global preparedness for future outbreaks.

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The paper "Structural basis for Ebola virus nucleocapsid assembly and function regulated by VP24" appeared on 10 March 2025 in Nature Communications, with doi: 10.1038/s41467-025-57236-4

Related video:

https://www.infront.kyoto-u.ac.jp/wp-content/uploads/2025/03/250310_野田研究室_movie.mp4

About Kyoto University

Kyoto University is one of Japan and Asia's premier research institutions, founded in 1897 and responsible for producing numerous Nobel laureates and winners of other prestigious international prizes. A broad curriculum across the arts and sciences at undergraduate and graduate levels complements several research centers, facilities, and offices around Japan and the world. For more information, please see: http://www.kyoto-u.ac.jp/en