9OCF

2.73A cryo-EM structure of the Measles Virus L-P in complex with ERdRp-0519

This is a non-PDB format compatible entry.

Summary for 9OCF

• Entry DOI: 10.2210/pdb9ocf/pdb
• EMDB information: 70313
• Descriptor: RNA-directed RNA polymerase L, Phosphoprotein, 2-methyl-~{N}-[4-[(2~{S})-2-(2-morpholin-4-ylethyl)piperidin-1-yl]sulfonylphenyl]-5-(trifluoromethyl)pyrazole-3-carboxamide (3 entities in total)
• Functional Keywords: measles virus, l protein, phosphoprotein, rna-dependent rna polymerase, prntase, gdp polyribonucleotidyl transferase, rna capping, mtase, viral replication, viral protein, transferase, erdrp-0519
• Biological source: Measles virus strain Edmonston-B; More
• Total number of polymer chains: 5
• Total formula weight: 464793.55

Authors

Liu, B.,Wang, D.,Yang, G. (deposition date: 2025-04-24, release date: 2025-09-03, Last modification date: 2025-10-29)

Primary citation

Wang, D.,Bu, F.,Yang, G.,Liu, B.
Structural basis of measles virus polymerase inhibition by nonnucleoside inhibitor ERDRP-0519.
Nat Commun, 16:9061-9061, 2025

PubMed Abstract: ERDRP-0519 is a potent nonnucleoside inhibitor active against measles virus (MeV) and other Morbilliviruses. Here we report cryo-EM structures of the compound bound to MeV polymerase complexes at 2.73 Å and 2.48 Å resolution, revealing a unique binding pocket in the RdRp palm subdomain that overlaps the catalytic GDN motif. These findings clarify the basis of resistance mutations, including W671, and provide a foundation for designing next-generation Paramyxovirus antivirals.

PubMed: 41083444
DOI: 10.1038/s41467-025-64128-0

Experimental method

ELECTRON MICROSCOPY (2.73 Å)