Influenza Genome Shield Decoded
Researchers mapped influenza’s RNA-protein shield at atomic scale, revealing drug targets to destabilize the viral genome.
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To combat the influenza virus, researchers are investigating ways to destabilize its genome, composed of eight RNA molecules. However, each RNA segment is bound to a complex assembly of proteins that forms a double-helix structure, shielding the viral genome and making it challenging to target.
For the first time, scientists have mapped this protective protein mantle and its interactions with the RNA at an atomic scale. This achievement, by a team from CNRS and Université Grenoble Alpes, addresses a longstanding gap in viral structural biology, which the scientific community has pursued for nearly 40 years.
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Subscribe for FREEUsing advanced biochemical methods and cryo-electron microscopy provided by the Integrated Structural Biology platform in Grenoble (CEA/CNRS/EMBL/Université Grenoble Alpes), the researchers have visualized the precise positioning of viral RNA within its protein coat. They also detailed the interactions between the two strands of the helical structure.
Cryo-electron microscopy
A technique that uses electron beams to visualize biological molecules at near-atomic resolutions under extremely cold temperatures. This preserves the structure of biological specimens and enables detailed imaging.RNA (ribonucleic acid)
A molecule that serves as the genetic material for certain viruses, including influenza. It is single-stranded and can encode instructions for viral replication.Protein coat
Also known as a capsid, this structure surrounds and protects the genetic material of a virus. In influenza, the coat forms a double-helix structure that binds tightly to RNA.A potential pathway for drug development
Understanding the atomic-scale arrangement of the RNA-protein assembly opens opportunities for designing antiviral drugs. By targeting the protein coat that protects viral RNA, novel therapeutic molecules could bind to and destabilize the genome, ultimately inhibiting the virus’s replication.
Influenza virus infections cause significant health burdens worldwide, including epidemics that affect millions of people annually. In France alone, the virus leads to between 2 and 6 million cases each winter, with approximately 10,000 deaths occurring among vulnerable populations.
Methodological advancements in structural biology
This milestone was achieved using state-of-the-art cryo-electron microscopy, a powerful tool for capturing biological structures at near-atomic resolutions. The Integrated Structural Biology platform enabled researchers to characterize intricate interactions that were previously elusive. By combining these high-resolution images with biochemical analysis, the team successfully unraveled the viral genome’s architecture.
This discovery represents a significant step toward developing treatments that exploit structural vulnerabilities in the influenza virus. Although the findings are currently at the molecular research stage, they provide critical information for future therapeutic design.
Reference: Chenavier F, Zarkadas E, Freslon LL, et al. Influenza a virus antiparallel helical nucleocapsid-like pseudo-atomic structure. Nucleic Acids Res. 2024:gkae1211. doi: 10.1093/nar/gkae1211
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