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TitleStructural mechanism of Borna disease virus 1 RNA polymerase autoinhibition and suramin-mediated inhibition.
Journal, issue, pagesCell Rep, Vol. 45, Issue 6, Page 117462, Year 2026
Publish dateMay 28, 2026
AuthorsKankan Yang / Haiqiang Wu / Zuxing Liang / Junwei Zou / Jun Ma /
PubMed AbstractBorna disease virus 1 (BoDV-1) is a neurotropic pathogen that causes severe, often fatal encephalitis, yet effective treatments remain unavailable. As a nuclear-replicating mononegavirus, BoDV-1 ...Borna disease virus 1 (BoDV-1) is a neurotropic pathogen that causes severe, often fatal encephalitis, yet effective treatments remain unavailable. As a nuclear-replicating mononegavirus, BoDV-1 employs a minimal L-P polymerase complex. Here, we report cryo-electron microscopy (cryo-EM) structures of the BoDV-1 polymerase in L-alone, apo-L-P, and inhibitor-bound L-P states, revealing the most compact L protein characterized among mononegaviruses. While the catalytic core is conserved, the C-terminal domains are degenerate, with the methyltransferase-like (MTase-like) domain lacking canonical functional motifs. We identify an N-terminal autoinhibitory element (AIE) that is positioned to physically block the template entry tunnel, suggesting an autoinhibition mechanism reminiscent of a "molecular plug." Furthermore, we demonstrate that the inhibitor suramin binds in a specific triple-molecule mode, potentially achieving inhibition by sterically occluding RNA access and allosterically restricting the catalytic core. These findings elucidate the architecture and regulation of the BoDV-1 polymerase, providing a structural framework for rational antiviral design.
External linksCell Rep / PubMed:42213784
MethodsEM (single particle)
Resolution2.7 - 2.83 Å
Structure data

66467

9x1v

EMDB-66467, PDB-9x1v:
Cryo-EM structure of Borna disease virus RNA polymerase complex
Method: EM (single particle) / Resolution: 2.72 Å

66473

9x28

EMDB-66473, PDB-9x28:
Cryo-EM structure of Borna disease virus RNA polymerase L protein
Method: EM (single particle) / Resolution: 2.83 Å

66595

9x5r

EMDB-66595, PDB-9x5r:
Cryo-EM structure of Borna disease virus RNA-directed RNA polymerase in complex with Suramin
Method: EM (single particle) / Resolution: 2.7 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-SVR:
8,8'-[CARBONYLBIS[IMINO-3,1-PHENYLENECARBONYLIMINO(4-METHYL-3,1-PHENYLENE)CARBONYLIMINO]]BIS-1,3,5-NAPHTHALENETRISULFON / medication*YM

Source
  • borna disease virus-v
KeywordsVIRAL PROTEIN / Polymerase / Phosphoprotein / PhosComplex / Complex / Inhibitor

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