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TitleStructures of the measles virus polymerase complex with non-nucleoside inhibitors and mechanism of inhibition.
Journal, issue, pagesCell, Year 2025
Publish dateJun 27, 2025
AuthorsYiru Wang / Lixia Zhao / Yi Zhang / Xiuxia Gao / Yannan Wang / Wenping Shi / Roger D Kornberg / Heqiao Zhang /
PubMed AbstractThe measles virus (MeV), a highly contagious non-segmented negative-sense RNA virus in the Paramyxoviridae family, causes millions of infections annually, with no approved antivirals available. The ...The measles virus (MeV), a highly contagious non-segmented negative-sense RNA virus in the Paramyxoviridae family, causes millions of infections annually, with no approved antivirals available. The viral polymerase complex, comprising the large (L) protein and the tetrameric phosphoprotein (P), is a key antiviral target. We determined the cryo-electron microscopy structures of the MeV polymerase complex alone and bound to two non-nucleoside inhibitors, ERDRP-0519 and AS-136A. Inhibitor binding induces a conformational change in the catalytic loop, allosterically locking the polymerase in an inactive "GDN-out" state. These findings led to the proposal that ERDRP-0519 would also be effective against Nipah virus (NiV), a highly pathogenic virus with no available antivirals. This proposal was confirmed by structure determination of the NiV polymerase complex and by inhibition of transcription.
External linksCell / PubMed:40628260
MethodsEM (single particle)
Resolution3.0 - 3.4 Å
Structure data

62459

9knq

EMDB-62459, PDB-9knq:
Measles virus L-P complex in apo state
Method: EM (single particle) / Resolution: 3.0 Å

62461

9knt

EMDB-62461: Polymerase complex-inhibitor IERDRP-0519-bound measles virus L-P complex
PDB-9knt: ERDRP-0519-bound measles virus L-P complex
Method: EM (single particle) / Resolution: 3.4 Å

62463

9knv

EMDB-62463, PDB-9knv:
AS-136A-bound measles virus L-P complex
Method: EM (single particle) / Resolution: 3.3 Å

62467

9knz

EMDB-62467, PDB-9knz:
ERDRP-0519-bound Nipah virus L-P complex
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-ZN:
Unknown entry

PDB-1ef9:
THE CRYSTAL STRUCTURE OF METHYLMALONYL COA DECARBOXYLASE COMPLEXED WITH 2S-CARBOXYPROPYL COA

PDB-1ega:
CRYSTAL STRUCTURE OF A WIDELY CONSERVED GTPASE ERA

Source
  • Measles virus (strain Ichinose-B95a)
  • measles virus strain ichinose-b95a
  • ParamyxoviridaeMeasles virus strain Ichinose-B95a
  • henipavirus nipahense
KeywordsTRANSCRIPTION / Measles virus / L-P complex / polymerase complex / nsNSV / cryo-EM / Complex / AS-136A / ERDRP-0519 / Nipah virus

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