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Breakthrough Research on Filoviruses Offers Hope for Universal Antiviral Drugs
Currently, the global arsenal against deadly filoviruses, such as Ebola and Marburg, is limited, with only one approved vaccine and specific antibody treatments available, and those only targeting single viral species.
Researchers at La Jolla Institute for Immunology (LJI) are pioneering efforts to develop new antiviral therapies through detailed molecular analysis of these viruses. By employing high-resolution imaging techniques, they are mapping the vulnerabilities within viral structures that could be targeted in future treatments.
A recent study published in Cell by scientists at LJI’s Center for Vaccine Innovation presents unprecedented, comprehensive images of the Ebola virus nucleocapsid. This discovery could significantly advance the creation of antivirals aimed at a variety of filoviruses simultaneously.
“A universal antiviral is the dream for stopping any kind of viral disease,” stated Reika Watanabe, Ph.D., a staff scientist at LJI and the study’s lead author. “This research moves us closer to realizing that dream.”
Understanding the Virus Structure
The Ebola virus utilizes its nucleocapsid—a complex structure that safeguards its genetic material—to replicate inside host cells and hinder the body’s immune response. This mechanism allows the virus to effectively convert infected cells into production centers for more viral particles.
Watanabe’s research achieved a notable milestone by using cryo-electron tomography to visualize the nucleocapsid in action within infected cells, an unprecedented accomplishment in the field.
Upon detailed observation, the Ebola virus nucleocapsid resembles a coiled telephone cord. Watanabe documented various stages of this coiling, highlighting a cylindrical shape composed of three distinct layers. Each layer serves a unique function during viral replication—a fact that had been unknown to scientists prior to this study.
Moreover, Watanabe’s investigation revealed the composition of the outer layer, demonstrating how it acts as a flexible connection between the nucleocapsid and the viral membrane.
“We found that the core protein assumes different forms in the various layers of the nucleocapsid to fulfill different roles,” remarked Erica Ollmann Saphire, Ph.D., MBA, LJI Professor and the study’s senior author.
Further analysis by Watanabe uncovered how proteins contact each other during nucleocapsid assembly in host cells and how the Ebola virus rearranges these proteins to form new viral particles.
“This study solves several puzzles in the field,” added Saphire.
Broader Implications for Filovirus Research
According to Watanabe, targeting the nucleocapsid could effectively halt the virus’s lifecycle. “If you don’t have a nucleocapsid, nothing can happen. That’s the core of the virus,” she explained.
The nucleocapsid’s fundamental role in the infection process suggests it may have retained its structural features throughout the evolution of filoviruses. This consistency, referred to as “conserved,” indicates its importance across various related species.
Notably, all known pathogenic filovirus species, including both Ebola and Marburg, exhibit a conserved nucleocapsid structure. Watanabe is now spearheading additional research to delve deeper into the nucleocapsid assembly in the Marburg virus, building on the insights gained from the Ebola study.
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