Interference with Ebola Replication Process Halts Growth and Kills Virus

Researchers from Washington University School of Medicine have identified a strategy to stop Ebola in its tracks, a disease that has already killed over 10,000 individuals in West Africa alone.

Researchers from Washington University School of Medicine have identified a strategy to stop Ebola in its tracks, a disease that has already killed over 10,000 individuals in West Africa alone.

The process involves interfering with the Ebola’s RNA protective coat, nucleoprotein, during replication in order to eliminate the virus.

As Senior Author Gaya Amarasinghe, PhD, assistant professor of pathology and immunology, and his colleagues explained in the study published on Cell Reports, the virus creates a protein that removes a protective coat from the genetic material. This gives it the opportunity to expose the viral genome so that it can be copied and put back into the virus’ makeup.

“This coat-check protein, known as VP35, has a great deal of potential as a new target for Ebola treatments,” Amarasinghe said in a news release. “If we can block this process, we can stop Ebola infection by blocking viral replication.”

The scientists tested the idea that while that protective coat is removed, they could interfere with a short chain of amino acids. The compound replaced the viral genome before it could be returned and the sequence was disrupted. As a result, the virus was unable to survive.

When the virus makes a copy, the new addition needs a protective coat of its own. The team found that VP35 was able to stop that from occurring as well so it further disabled Ebola.

For the past 7 years, Amarasinghe, Leung, and colleagues collaborated to find how VP35 fits into the nucleoprotein replication process.

“One of the major challenges was that the part of VP35 involved in this interaction is an intrinsically disordered peptide,” First Author Daisy Leung, PhD, also an assistant professor of pathology and immunology, said. “This means that it may not take on a definite structure until it binds to another protein. That made structural studies of VP35 difficult because the structure, which plays a critical role in determining function, doesn’t form without its specific binding partner.”

However, their research proved that the protein binds to the virus’ nucleoprotein and stops the process of copying the genome — a discovery that leads the way to better treatments.

“Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development,” the team concluded in the study.