Structural basis of measles virus polymerase inhibition by nonnucleoside inhibitor ERDRP-0519.

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.

SUBMITTER: Wang D 

PROVIDER: S-EPMC12518664 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature