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TitleStructural basis for the activation of plant bunyavirus replication machinery and its dual-targeted inhibition by ribavirin.
Journal, issue, pagesNat Plants, Vol. 11, Issue 3, Page 518-530, Year 2025
Publish dateMar 5, 2025
AuthorsJia Li / Lei Cao / Yaqian Zhao / Jinghan Shen / Lei Wang / Mingfeng Feng / Min Zhu / Yonghao Ye / Richard Kormelink / Xiaorong Tao / Xiangxi Wang /
PubMed AbstractDespite the discovery of plant viruses as a new class of pathogens over a century ago, the structure of plant virus replication machinery and antiviral pesticide remains lacking. Here we report five ...Despite the discovery of plant viruses as a new class of pathogens over a century ago, the structure of plant virus replication machinery and antiviral pesticide remains lacking. Here we report five cryogenic electron microscopy structures of a ~330-kDa RNA-dependent RNA polymerase (RdRp) from a devastating plant bunyavirus, tomato spotted wilt orthotospovirus (TSWV), including the apo, viral-RNA-bound, base analogue ribavirin-bound and ribavirin-triphosphate-bound states. They reveal that a flexible loop of RdRp's motif F functions as 'sensor' to perceive viral RNA and further acts as an 'adaptor' to promote the formation of a complete catalytic centre. A ten-base RNA 'hook' structure is sufficient to trigger major conformational changes and activate RdRp. Chemical screening showed that ribavirin is effective against TSWV, and structural data revealed that ribavirin disrupts both hook-binding and catalytic core formation, locking polymerase in its inactive state. This work provides structural insights into the mechanisms of plant bunyavirus RdRp activation and its dual-targeted site inhibition, facilitating the development of pesticides against plant viruses.
External linksNat Plants / PubMed:40044941 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 4.0 Å
Structure data

37252

8ki6

EMDB-37252, PDB-8ki6:
Structure of tomato spotted wilt virus L protein binding to Ribavirin
Method: EM (single particle) / Resolution: 3.4 Å

37253

8ki7

EMDB-37253, PDB-8ki7:
Structure of Tomato spotted wilt virus L protein contained endoH domain binding to 3'5'vRNA
Method: EM (single particle) / Resolution: 3.7 Å

37254

8ki8

EMDB-37254, PDB-8ki8:
structure of Tomato spotted wilt virus L protein binding to 5'vRNA
Method: EM (single particle) / Resolution: 3.2 Å

37255

8ki9

EMDB-37255, PDB-8ki9:
Structure of Tomato spotted wilt virus L protein contained CTD
Method: EM (single particle) / Resolution: 4.0 Å

37256

8kia

EMDB-37256, PDB-8kia:
Tomato spotted wilt virus L protein (apo state)
Method: EM (single particle) / Resolution: 4.0 Å

61241

9j8v

EMDB-61241, PDB-9j8v:
TSWV L protein in complex with ribavirin 5-triphosphate
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-RBV:
1-(beta-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide / medication, antivirus*YM

ChemComp-RTP:
RIBAVIRIN TRIPHOSPHATE

Source
  • orthotospovirus tomatomaculae
  • tomato spotted wilt virus (strain bulgarian l3)
  • synthetic construct (others)
KeywordsVIRAL PROTEIN / tomato spotted wilt virus / L protein / VIRAL PROTEIN/RNA / VIRAL PROTEIN-RNA complex / TSWV / ribavirin 5-triphosphate

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