Crystal structure of aura virus capsid protease and its complex with dioxane: new insights into capsid-glycoprotein molecular contacts.
Authors: Aggarwal Megha, Tapas Satya, Preeti, Siwach Anjul, Kumar Pravindra, Kuhn Richard J, Tomar Shailly
Journal: PloS one
Summary
# Editorial Summary: Aura Virus Capsid-Glycoprotein Interactions Understanding how alphaviruses assemble and bud from infected cells requires detailed knowledge of the molecular contacts between the viral capsid core and the envelope glycoproteins E1 and E2—interactions that are fundamental to the virus life cycle. Researchers determined high-resolution crystal structures of the Aura virus capsid protease and its complex with dioxane, then used these structures alongside homology models and cryo-electron microscopy density maps of Venezuelan equine encephalitis virus to map the precise interface between capsid and glycoproteins. Key findings identified that the E2 glycoprotein endodomain adopts a helix-loop-helix motif, with the loop region inserting into a hydrophobic pocket on the capsid protein surface; within this loop, the amino acid proline at position 405 makes critical hydrophobic contacts with the capsid, stabilised by nearby cysteine and tyrosine residues that anchor the E2 structure itself. The dioxane molecule in the capsid protease complex occupied and structurally mimicked this same hydrophobic pocket, effectively replicated the interactions normally made by the E2 proline residue. For equine professionals, these structural insights into alphavirus assembly mechanisms lay groundwork for understanding viral pathogenesis in diseases such as Venezuelan equine encephalitis and may ultimately inform development of antiviral therapeutics or vaccine strategies targeting capsid-glycoprotein interactions.
Read the full abstract on PubMed
Practical Takeaways
- •This is fundamental virology research with no direct clinical application to equine practice
- •Findings may inform future antiviral development targeting equine alphaviruses like VEEV, but this is distant from current clinical tools
- •Understanding viral capsid-glycoprotein interactions at molecular level could eventually support vaccine or therapeutic development against Venezuelan equine encephalitis in horses
Key Findings
- •Crystal structures of Aura virus capsid protease determined at 1.81 and 1.98 Å resolution showing hydrophobic pocket responsible for glycoprotein interaction
- •E2 endodomain contains helix-loop-helix motif with loop region fitting into capsid protein hydrophobic pocket
- •Pro405 residue in E2 endodomain loop makes critical intermolecular hydrophobic contacts with capsid for virus stability
- •Dioxane ligand structurally mimics Pro405 pyrollidine ring, demonstrating potential for structure-based antiviral drug design