Structural basis for the activation of plant bunyavirus replication machinery and its dual-targeted inhibition by ribavirin.

ABSTRACT: 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 r

SUBMITTER: Li J 

PROVIDER: S-EPMC11928317 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature